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Human intestinal microbial metabolism of naringin

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Abstract

Naringin, a major flavonoid in citrus fruits, has been proved to be a promising antitussive candidate. It undertakes complicated metabolism. In this study, human intestinal microbial metabolism of naringin was studied in vitro. Six persons’ fecal water, which have intestinal microbial enzyme, were used in the first experiment. Naringin was metabolized by fecal water into naringenin. Subsequently, 3-(4-hydroxyphenyl)propionic acid (4-HPPA) was produced with naringenin degradation by a person’s fecal water. However, 4-HPPA was not detected after naringenin degradation by the other 5 subjects’ fecal water and the reason might be that the degrading velocity of 4-HPPA exceeded the producing velocity. To confirm the difference in degrading 4-HPPA among human feces, 22 healthy persons’ feces were used for incubation. In this second experiment, 15 persons’ feces could degrade 4-HPPA, but the other 7 subjects’ could not. Human feces showed different ability of degrading 4-HPPA, and there are no gender differences. These results may be helpful for explaining findings in pharmacological and toxicological studies and are groundwork for clinical studies.

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References

  • Aura AM (2008) Microbial metabolism of dietary phenolic compounds in the colon. Phytochem Rev 7:407–429

    Article  CAS  Google Scholar 

  • Aura AM, O’Leary KA, Williamson G, Ojala M, Bailey M, Puupponen-Pimia R, Nuutila AM, Oksman-Caldentey KM, Poutanen K (2002) Quercetin derivatives are deconjugated and converted to hydroxyphenylacetic acids but not methylated by human fecal flora in vitro. J Agric Food Chem 50(6):1725–1730

    Article  CAS  PubMed  Google Scholar 

  • Chen YT, Zheng RL, Jia ZJ, Ju Y (1990) Flavonoids as superoxide scavengers and antioxidants. Free Radic Biol Med 9(1):19–21

    Article  PubMed  Google Scholar 

  • Clavel T, Henderson G, Alpert CA, Philippe C, Rigottier-Gois L, Dore J, Blaut M (2005) Intestinal bacterial communities that produce active estrogen-like compounds enterodiol and enterolactone in humans. Appl Environ Microbiol 71(10):6077–6085. doi:10.1128/AEM.71.10.6077-6085.2005

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Clavel T, Borrmann D, Braune A, Dore J, Blaut M (2006) Occurrence and activity of human intestinal bacteria involved in the conversion of dietary lignans. Anaerobe 12(3):140–147. doi:10.1016/j.anaerobe.2005.11.002

    Article  CAS  PubMed  Google Scholar 

  • Diaz E, Ferrandez A, Prieto MA, Garcia JL (2001) Biodegradation of aromatic compounds by Escherichia coli. Microbiol Mol Biol Rev 65(4):523–569. doi:10.1128/MMBR.65.4.523-569.2001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gao S, Li P, Yang H, Fang S, Su W (2011) Antitussive effect of naringin on experimentally induced cough in Guinea pigs. Planta Med 77(1):16–21. doi:10.1055/s-0030-1250117

    Article  CAS  PubMed  Google Scholar 

  • Griffiths LA, Barrow A (1972) Metabolism of flavonoid compounds in germ-free rats. Biochem J 130(4):1161–1162

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Guyton AC, Hall JE (ed) (1996) Gastrointestinal physiology. Textbook of Medical Physiology, 9th edn. Philadelphia

  • Herles C, Braune A, Blaut M (2004) First bacterial chalcone isomerase isolated from Eubacterium ramulus. Arch Microbiol 181(6):428–434

    Article  CAS  PubMed  Google Scholar 

  • Kim DH, Jung EA, Sohng IS, Han JA, Kim TH, Han MJ (1998) Intestinal bacterial metabolism of flavonoids and its relation to some biological activities. Arch Pharm Res 21(1):17–23

    Article  CAS  PubMed  Google Scholar 

  • Lee CH, Jeong TS, Choi YK, Hyun BH, Oh GT, Kim EH, Kim JR, Han JI, Bok SH (2001) Anti-atherogenic effect of citrus flavonoids, naringin and naringenin, associated with hepatic ACAT and aortic VCAM-1 and MCP-1 in high cholesterol-fed rabbits. Biochem Biophys Res Commun 284(3):681–688. doi:10.1006/bbrc.2001.5001

    Article  CAS  PubMed  Google Scholar 

  • Liu M, Yang C, Zou W, Guan X, Zheng W, Lai L, Fang S, Cai S, Su W (2011a) Toxicokinetics of naringin, a putative antitussive, after 184-day repeated oral administration in rats. Environ Toxicol Pharmacol 31(3):485–489. doi:10.1016/j.etap.2011.01.006

    Article  PubMed  Google Scholar 

  • Liu Y, Wu H, Nie YC, Chen JL, Su WW, Li PB (2011b) Naringin attenuates acute lung injury in LPS-treated mice by inhibiting NF-kappaB pathway. Int Immunopharmacol 11(10):1606–1612. doi:10.1016/j.intimp.2011.05.022

    Article  CAS  PubMed  Google Scholar 

  • Liu M, Zou W, Yang C, Peng W, Su W (2012) Metabolism and excretion studies of oral administered naringin, a putative antitussive, in rats and dogs. Biopharm Drug Dispos 33(3):123–134. doi:10.1002/bdd.1775

    Article  PubMed  Google Scholar 

  • Luo YL, Zhang CC, Li PB, Nie YC, Wu H, Shen JG, Su WW (2012) Naringin attenuates enhanced cough, airway hyperresponsiveness and airway inflammation in a guinea pig model of chronic bronchitis induced by cigarette smoke. Int Immunopharmacol 13(3):301–307. doi:10.1016/j.intimp.2012.04.019

    Article  CAS  PubMed  Google Scholar 

  • Martin MJ, Marhuenda E, Perez-Guerrero C, Franco JM (1994) Antiulcer effect of naringin on gastric lesions induced by ethanol in rats. Pharmacology 49(3):144–150

    Article  CAS  PubMed  Google Scholar 

  • Nemeth K, Plumb GW, Berrin JG, Juge N, Jacob R, Naim HY, Williamson G, Swallow DM, Kroon PA (2003) Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr 42(1):29–42. doi:10.1007/s00394-003-0397-3

    Article  CAS  PubMed  Google Scholar 

  • Nie YC, Wu H, Li PB, Luo YL, Long K, Xie LM, Shen JG, Su WW (2012a) Anti-inflammatory effects of naringin in chronic pulmonary neutrophilic inflammation in cigarette smoke-exposed rats. J Med Food 15(10):894–900. doi:10.1089/jmf.2012.2251

    Article  CAS  PubMed  Google Scholar 

  • Nie YC, Wu H, Li PB, Xie LM, Luo YL, Shen JG, Su WW (2012b) Naringin attenuates EGF-induced MUC5AC secretion in A549 cells by suppressing the cooperative activities of MAPKs-AP-1 and IKKs-IkappaB-NF-kappaB signaling pathways. Eur J Pharmacol 690(1–3):207–213. doi:10.1016/j.ejphar.2012.06.040

    Article  CAS  PubMed  Google Scholar 

  • Nikolic D, van Breemen RB (2004) New metabolic pathways for flavanones catalyzed by rat liver microsomes. Drug Metab Dispos 32(4):387–397. doi:10.1124/dmd.32.4.38732/4/387

    Article  CAS  PubMed  Google Scholar 

  • Rechner AR, Smith MA, Kuhnle G, Gibson GR, Debnam ES, Srai SK, Moore KP, Rice-Evans CA (2004) Colonic metabolism of dietary polyphenols: influence of structure on microbial fermentation products. Free Radic Biol Med 36(2):212–225

    Article  CAS  PubMed  Google Scholar 

  • Schindler R, Mentlein R (2006) Flavonoids and vitamin E reduce the release of the angiogenic peptide vascular endothelial growth factor from human tumor cells. J Nutr 136(6):1477–1482

    CAS  PubMed  Google Scholar 

  • Schneider H, Blaut M (2000) Anaerobic degradation of flavonoids by Eubacterium ramulus. Arch Microbiol 173(1):71–75

    Article  CAS  PubMed  Google Scholar 

  • Walle T, Walle UK, Halushka PV (2001) Carbon dioxide is the major metabolite of quercetin in humans. J Nutr 131(10):2648–2652

    CAS  PubMed  Google Scholar 

  • Walle T, Browning AM, Steed LL, Reed SG, Walle UK (2005) Flavonoid glucosides are hydrolyzed and thus activated in the oral cavity in humans. J Nutr 135(1):48–52

    CAS  PubMed  Google Scholar 

  • Wang LQ, Meselhy MR, Li Y, Nakamura N, Min BS, Qin GW, Hattori M (2001) The heterocyclic ring fission and dehydroxylation of catechins and related compounds by Eubacterium sp. strain SDG-2, a human intestinal bacterium. Chem Pharm Bull (Tokyo) 49(12):1640–1643

    Article  CAS  Google Scholar 

  • Yu KU, Jang IS, Kang KH, Sung CK, Kim DH (1997) Metabolism of saikosaponin c and naringin by human intestinal bacteria. Arch Pharm Res 20(5):420–424. doi:10.1007/BF02973933

    Article  CAS  PubMed  Google Scholar 

  • Zou W, Yang C, Liu M, Su W (2012) Tissue distribution study of naringin in rats by liquid chromatography-tandem mass spectrometry. Arzneimittelforschung 62(4):181–186. doi:10.1055/s-0031-1299746

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors appreciate the financial support from the National Major Scientific and Technical Special Project of China (No. 2011ZX09102-011-03).

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Correspondence to Weiwei Su or Kejian Zhang.

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Zou, W., Luo, Y., Liu, M. et al. Human intestinal microbial metabolism of naringin. Eur J Drug Metab Pharmacokinet 40, 363–367 (2015). https://doi.org/10.1007/s13318-014-0193-x

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