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


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.


  1. 1.

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

  2. 2.

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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 21.

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

  22. 22.

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

  23. 23.

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

  24. 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.

  25. 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.

  26. 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.

  27. 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.

  28. 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.

  29. 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.

  30. 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.

  31. 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.

  32. 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.

  33. 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.

  34. 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.

  35. 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.

  36. 36.

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

  37. 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.

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Correspondence to Yun-Bae Kim.

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Kim, T., 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).

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