Skip to main content
Download PDF

Comparative analysis of anti-Helicobacter pylori activities of FEMY-R7 composed of Laminaria japonica and Oenothera biennis extracts in mice and humans

Laboratory Animal Research volume 31, pages 7–12 (2015)Cite this article

Abstract

Helicobacter pylori-eliminating effects of FEMY-R7, composed of Laminaria japonica and Oenothera biennis extracts, were investigated in mice and humans. Male C57BL/6 mice were infected with the bacteria by intragastric inoculation (1×109 CFU/mouse) 3 times at 2-day intervals, and simultaneously, orally treated twice a day with total 20, 64 or 200 mg/kg/day FEMY-R7 for 2 weeks. In Campylobcter-like organism (CLO)-detection tests on gastric mucosa and feces, FEMY-R7 reduced the urease-positive reactivity in a dose-dependent manner; i.e., the positivity ratios were decreased to 70, 20, and 10% for gastric mocosa and to 80, 50, and 20% for feces. In a clinical sudy, human subjects, confirmed to be infected with Helicobacter pylori, were orally administered twice a day with capsules containing total 100, 320 or 1,000 mg/man/day FEMY-R7 (matching doses for 20, 64 or 200 mg/kg/day, respectively, in mice from a body surface area-based dose translation) for 8 weeks. FEMY-R7 decreased the positivity ratios in feces to 70, 40, and 30%, respectively. In bacterial culture, H. pylori was identified from the CLO-positive stools of mice and humans. The bacterial identification ratios exhibited a good correlation between the matching doses in mice and humans. It is suggested that FEMY-R7 could be a promising functional food without tolerance as an adjunct to reduce the dosage of antibiotics for the treatment of recurrent H. pylori infection.

References

  1. Wallace IL, Granger DN. The cellular and molecular basis of gastric mucosal defense. FASEB J 1996; 10(7): 731–740.

    Article  CAS  PubMed  Google Scholar 

  2. Neal MJ. Medical Pharmacology at a Glance. 3rd ed, Blackwell Publishing Inc, London, 2003; pp 30–31.

    Google Scholar 

  3. Isobe H, Okajima K, Harada N, Liu W, Okabe H. Activated protein C reduces stress-induced gastric mucosal injury in rats by inhibiting the endothelial cell injury. J Thromb Haemost 2004; 2(2): 313–320.

    Article  CAS  PubMed  Google Scholar 

  4. Byun SK, Lee YE, Shin SH, Jang JY, Choi BI, Park DS, Jeon JH, Nahm SS, Hwang SY, Kim YB. The role of corticosteroids in stress-induced gastric ulceration in rats. Lab Anim Res 2007; 23(2): 127–131.

    Google Scholar 

  5. Slomiany BL, Piotrowski J, Slomiany A. Induction of tumor necrosis factor-alpha and apoptosis in gastric mucosal injury by indomethacin: effect of omeprazole and ebrotidine. Scand J Gastroenterol 1997; 32(7): 638–642.

    Article  CAS  PubMed  Google Scholar 

  6. Filaretova L, Tanaka A, Miyazawa T, Kato S, Takeuchi K. Mechanisms by which endogenous glucocorticoid protects against indomethacin-induced gastric injury in rats. Am J Physiol Gastrointest Liver Physiol 2002; 283(5): 1082–1089.

    Article  Google Scholar 

  7. Cao H, Wang MW, Jia JH, Wang QG, Cheng MS. Comparison of the effects of pantoprazole enantimers on gastric mucosal lesions and gastric epithelial cells in rats. J Health Sci 2004; 50(1): 1–8.

    Article  CAS  Google Scholar 

  8. Rao ChV, Ojha SK, Radhakrishnan K, Govindarajan R, Rastogi S, Mehrotra S, Pushpangadan P. Antiulcer activity of Utleria salicifolia rhizome extract. J Ethnopharmacol 2004; 91(2-3): 243–249.

    Article  PubMed  Google Scholar 

  9. Kim YR, Lee MR, Kim YH, Jang BJ, Park SC, Han SH, Kim BH, Ryoo ZY, Kim KS. Effect of Opuntiahumifusa extract on indomethacin-induced gastric ulcer in Sprague Dawley rat. Lab Anim Res 2005; 21(4): 375–578.

    Google Scholar 

  10. Raffin RP, Colomé LM, Schapoval EE, Jornada DS, Pohlmann AR, Guterres SS. Gastro-resistant microparticles containing sodium pantoprazole: stability and in vivo anti-ulcer activity. Open Drug Deliv J 2007; 1:28–35.

    Article  CAS  Google Scholar 

  11. Dias PC, Foglio MA, Possenti A, de Carvalho JE. Antiulcerogenic activity of crude hydroalcoholic extract of Rosmarinus officinalis L. J Ethnopharmacol 2000; 69(1): 57–62.

    Article  CAS  PubMed  Google Scholar 

  12. Cantarella G, Martinez G, Cutuli VM, Loreto C, D’Alcamo M, Prato A, Amico-Roxas M, Bernardini R, Clementi G. Adrenomedullin modulates COX-2 and HGF expression in reserpine-injuried gastric mucosa in the rat. Eur J Pharmacol 2005; 518(2-3): 221–226.

    Article  CAS  PubMed  Google Scholar 

  13. Cantarella G, Martinez G, Di Benedetto G, Loreto C, Musumeci G, Prato A, Lempereur L, Matera M, Amico-Roxas M, Bernardini R, Clementi G Protective effects of amylin on reserpine-induced gastric damage in the rat. Pharmacol Res 2007; 56(1): 27–34.

    Article  CAS  PubMed  Google Scholar 

  14. Işbil Büyükcoşkun N, Güleç G, Ozlük K. Protective effect of centrally-injected glucagon-like peptide-1 on reserpine-induced gastric mucosal lesions in rat: possible mechanisms. Turk J Gastroenterol 2006; 17(1): 1–6.

    PubMed  Google Scholar 

  15. Pope AJ, Toseland CD, Rushant B, Richardson S, McVey M, Hills J. Effect of potent urease inhibitor, fluorofamide, on Helicobacter sp. in vivo and in vitro. Dig Dis Sci 1998; 43(1): 109–119.

    Article  CAS  PubMed  Google Scholar 

  16. Hahm KB, Kim DH, Lee KM, Lee JS, Surh YJ, Kim YB, Yoo BM, Kim JH, Joo HJ, Cho YK, Nam KT, Cho SW Effect of long-term administration of rebamipide on Helicobacter pylori infection in mice. Aliment Pharmacol Ther 2003; 18(Suppl 1): 24–38.

    Article  CAS  PubMed  Google Scholar 

  17. Aristoteli LP, O’Rourke JL, Danon S, Larsson H, Mellgard B, Mitchell H, Lee A. Urea, fluorofamide, and omeprazole treatments alter helicobacter colonization in the mouse gastric mucosa. Helicobacter 2006; 11(5): 460–468.

    Article  CAS  PubMed  Google Scholar 

  18. Coghlan JG, Gilligan D, Humphries H, McKenna D, Dooley C, Sweeney E, Keane C, O’ Morain C. Campylobacter pylori and recurrence of duodenal ulcers—a 12-month follow-up study. Lancet 1987; 2(8568): 1109–1111.

    Article  CAS  PubMed  Google Scholar 

  19. Graham DY, Evans DG, Evans DJ Jr. Campylobacter pylori. The organism and its clinical relevance. J Clin Gastroenterol 1989; 11(Suppl 1): S43–S48.

    PubMed  Google Scholar 

  20. Wotherspoon AC, Ortiz-Hidalgo C, Falzon MR, Isaacson PG. Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet 1991; 338(8776): 1175–1176.

    Article  CAS  PubMed  Google Scholar 

  21. Cover TL, Blaser MJ. Helicobacter pylori and gastroduodenal disease. Annu Rev Med 1992; 43: 135–145.

    Article  CAS  PubMed  Google Scholar 

  22. Lee A, Fox J, Hazell S. Pathogenicity of Helicobacter pylori: a perspective. Infect Immun 1993; 61(5): 1601–1610.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Marshall BJ. Helicobacter pylori in peptic ulcer: have Koch’s postulates been fulfilled? Ann Med 1995; 27(5): 565–568.

    Article  CAS  PubMed  Google Scholar 

  24. Zhang Z, Liu ZQ, Zheng PY, Tang FA, Yang PC. Influence of efflux pump inhibitors on the multidrug resistance of Helicobacter pylori. World J Gastroenterol 2010; 16(10): 1279–1284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Feldman SC, Reynaldi S, Stortz CA, Cerezo AS, Damont EB. Antiviral properties of fucoidan fractions from Leathesia difformis. Phytomedicine 1999; 6(5): 335–340.

    Article  CAS  PubMed  Google Scholar 

  26. Wang J, Zhang Q, Zhang Z, Song H, Li P. Potential antioxidant and anticoagulant capacity of low molecular weight fucoidan fractions extracted from Laminaria japonica. Int J Biol Macromol 2010; 46(1): 6–12.

    Article  CAS  PubMed  Google Scholar 

  27. Bojakowski K, Abramczyk P, Bojakowska M, Zwoliñska A, Przybylski J, Gaciong Z. Fucoidan improves the renal blood flow in the early stage of renal ischemia/reperfusion injury in the rat. J Physiol Pharmacol 2001; 52(1): 137–143.

    CAS  PubMed  Google Scholar 

  28. Li N, Zhang Q, Song J. Toxicological evaluation of fucoidan extracted from Laminaria japonica in Wistar rats. Food Chem Toxicol 2005; 43(3): 421–426.

    Article  PubMed  Google Scholar 

  29. Shibata H, Iimuro M, Uchiya N, Kawamori T, Nagaoka M, Ueyama S, Hashimoto S, Yokokura T, Sugimura T, Wakabayashi K. Preventive effects of Cladosiphon fucoidan against Helicobacter pylori infection in Mongolian gerbils. Helicobacter 2003; 8(1): 59–65.

    Article  CAS  PubMed  Google Scholar 

  30. Shibata H, KimuraTakagi I, Nagaoka M, Hashimoto S, Sawada H, Ueyama S, Yokokura T Inhibitory effect of Cladosiphon fucoidan on the adhesion of Helicobacter pylori to human gastric cells. J Nutr Sci Vitaminol 1999; 45(3): 325–336.

    Article  CAS  PubMed  Google Scholar 

  31. Funatogawa K, Hayashi S, Shimomura H, Yoshida T, Hatano T, Ito H, Hirai Y Antibacterial activity of hydrolyzable tannins derived from medicinal plants against Helicobacter pylori. Microbiol Immunol 2004; 48(4): 251–261.

    Article  CAS  PubMed  Google Scholar 

  32. Kamiya S, Osaki T, Yamaguci H, Shimada T, Okada T, Takahashi Y. Effect of evening primrose extract on growth, adhesion and colonization of Helicobacter pylori. Bact Adherence Bofilm 2003; 17: 16–19.

    Google Scholar 

  33. Cai J, Kim TS, Jang JY, Kim J, Shin K, Lee SP, Choi EK, Kim SH, Park M, Kim JB, Kim YB. In vitro and in vivo antiHelicobacter pylori activities of FEMY-R7 composed of fucoidan and evening primrose extract. Lab Anim Res 2014; 30(1): 28–34.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kim TS, Choi EK, Kim J, Shin K, Lee SP, Choi Y, Jeon JH, Kim YB. Anti-Helicobacter pylori activities of FEMY-R7 composed of fucoidan and evening primrose extract in mice and humans. Lab Anim Res 2014; 30(3): 131–135.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Yang YH, Park D, Yang G, Lee SH, Bae DK, Kyung J, Kim D, Choi EK, Son JC, Hwang SY, Kim YB. Anti-Helicobacter pylori effects of IgY from egg york of immunized hens. Lab Anim Res 2012; 28(1): 55–60.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J 2008; 22(3): 659–661.

    Article  CAS  PubMed  Google Scholar 

  37. Daw MA, Deegan P, Leen E, O’Morâin C. Short report: the effect of omeprazole on Helicobacter pylori and associated gastritis. Aliment Pharmacol Ther 1991; 5(4): 435–439.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. These two authors contributed equally to this work.

Authors and Affiliations

  1. Misuba RTech Co., Ltd., Asan, Korea

    Tae-Su Kim & Sung-Pyo Lee

  2. College of Veterinary Medicine, Chungbuk National University, 1 Chungdaero (Gaesin-dong), Cheongju, Chungbuk, 362-763, Korea

    Kyungha Shin, Ehn-Kyoung Choi, Youngjin Choi & Yun-Bae Kim

  3. Haewon Biotech Inc., Seoul, Korea

    Joseph H. Jeon

  4. Central Research Institute, Dr. Chung’s Food Co. Ltd., Chungbuk, Korea

    Yoon-Bok Lee

Authors
  1. Tae-Su Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyungha Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joseph H. Jeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ehn-Kyoung Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Youngjin Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sung-Pyo Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yoon-Bok Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yun-Bae Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yun-Bae Kim.

Rights and permissions

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kim, TS., Shin, K., Jeon, J.H. et al. Comparative analysis of anti-Helicobacter pylori activities of FEMY-R7 composed of Laminaria japonica and Oenothera biennis extracts in mice and humans. Lab Anim Res 31, 7–12 (2015). https://doi.org/10.5625/lar.2015.31.1.7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.5625/lar.2015.31.1.7

Keywords

  • Helicobacter pylori
  • FEMY-R7
  • Laminaria japonica
  • Oenothera biennis
  • Campylobcter-like organism-detection test
  • bacterial identification

Laboratory Animal Research

ISSN: 2233-7660