Effect of the flavonoid quercetin on inflammation and lipid peroxidation induced by Helicobacter pylori in gastric mucosa of guinea pig

  • Rodolfo González-Segovia
  • J. Luis Quintanar
  • Eva Salinas
  • Rebeca Ceballos-Salazar
  • Francisco Aviles-Jiménez
  • Javier Torres-López
Alimmentary Tract



Helicobacter pylori infection induces an inflammatory response in the gastric mucosa. Activation of polymorphonuclear leukocytes can produce oxidative damage to gastric tissue through intermediary radicals of oxygen and nitrogen. Vegetable extracts containing polyphenols of the flavonoid family have antibacterial activity, and the flavonoid quercetin possesses anti-H. pylori activity in vitro. The aim of this study was to analyze the effect of oral administration of pure quercetin on inflammation and lipid peroxidation induced by H. pylori in the gastric mucosa of the guinea pig.


Sixty days after oral infection with H. pylori guinea pigs received 200 mg/kg of quercetin daily by mouth for 15 days. The infiltration index of inflammatory cells and bacterial density in both the pyloric antrum and corpus were histologically determined by myeloperoxidase histochemistry, hematoxylin-eosin, and modified Giemsa stains. The lipid hydroperoxide content was assessed by the orange xylenol spectrophotometric method.


Quercetin significantly reduced the infiltration index of mononuclear cell and bacterial colonization in the pyloric antrum and corpus. In the antrum of infected quercetin-treated animals, a significant diminution of neutrophil leukocyte infiltration was observed compared with the infected nonquercetin-treated animals. In the antrum, the lipid hydroperoxide concentration was significantly decreased in infected animals treated with quercetin, whereas in the corpus no significant differences were observed.


Our results indicate that in vivo oral quercetin administration decreases H. pylori infection in the gastric mucosa and reduces both the inflammatory response and lipid peroxidation.

Key words

neutrophil leukocytes myeloperoxidase oxidative stress gastritis 


  1. 1.
    Supajatura V, Ushio H, Wada A, Yahiro K, Okumura K, Ogawa H, et al. Cutting edge: VacA, a vacuolating cytotoxin of Helicobacter pylori, directly activates mast cells for migration and production of proinflammatory cytokines. J Immunol 2002;168:2603–2607.PubMedGoogle Scholar
  2. 2.
    Brandt S, Kwok T, Hartig R, König W, Backert S. NF-kappaB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein. Proc Natl Acad Sci USA 2005;102:9300–9305.PubMedCrossRefGoogle Scholar
  3. 3.
    Zhao Y, Yokota K, Ayada K, Yamamoto Y, Okada T, Shen L, et al. Helicobacter pylori heat-shock protein 60 induces interleukin-8 via a Toll-like receptor (TLR) 2 and mitogenactivated protein (MAP) kinase pathway in human monocytes. J Med Microbiol 2007;56:154–164.PubMedCrossRefGoogle Scholar
  4. 4.
    Shimada T, Terano A, Chemokine expression in Helicobacter pylori-infected gastric mucosa. J Gastroenterol 1998;33:613–617.PubMedCrossRefGoogle Scholar
  5. 5.
    Peek RM. Helicobacter pylori strain-specific activation of signal transduction cascades related to gastric inflammation. Am J Physiol Gastrointest Liver Physiol 2001;280:525–530.Google Scholar
  6. 6.
    Aydemir SA, Tekin IO, Numanoglu G, Borazan A, Ustundag Y. Eosinophil infiltration, gastric juice and serum eosinophil cationic protein levels in Helicobacter pylori-associated chronic gastritis and gastric ulcer. Mediators Inflamm 2004;13:369–372.PubMedCrossRefGoogle Scholar
  7. 7.
    Ernst P. Review article: the role of inflammation in the pathogenesis of gastric cancer. Aliment Pharmacol Ther 1999;13:13–18.PubMedCrossRefGoogle Scholar
  8. 8.
    Dekigai H., Murakami M, Kita T. Mechanism of Helicobacter pylori-associated gastric mucosal injury. Dig Dis Sci 1995;40:1332.PubMedCrossRefGoogle Scholar
  9. 9.
    Yoshikawa T, Naito Y. The role of neutrophils and inflammation in gastric mucosal injury. Free Radic Res 2000;33:785–794.PubMedCrossRefGoogle Scholar
  10. 10.
    Stamatis G, Kyriazopoulos P, Golegou S, Basayiannis A, Skaltsas S, Skaltsa H. In vitro anti-Helicobacter pylori activity of Greek herbal medicines. J Ethnopharmacol 2003;88:175–179.PubMedCrossRefGoogle Scholar
  11. 11.
    Sung-Sook C, Dhiraj A. Vattem, Yuan-Tong L, Kalidas S. Phenolic antioxidants from clonal oregano (Origanum vulgare) with antimicrobial activity against Helicobacter pylori. Process Biochem 2005;40:809–816.CrossRefGoogle Scholar
  12. 12.
    Ustün O, Ozçelik B, Akyön Y, Abbasoglu U, Yesilada E. Flavonoids with anti-Helicobacter pylori activity from Cistus laurifolius leaves. J Ethnopharmacol 2006;108:457–461.PubMedCrossRefGoogle Scholar
  13. 13.
    Kuo SM, Leavitt PS, Lin CP. Dietary flavonoids interact with trace metals and affect metallothionein level in human intestinal cells. Biol Trace Elem Res 1998;62:135–153.PubMedCrossRefGoogle Scholar
  14. 14.
    Suzuki Y, Ishihara M, Segami T, Ito M. Anti-ulcer effects of antioxidants, quercetin, alpha-tocopherol, nifedipine and tetracycline in rats. Jpn J Pharmacol 1998;78:435–441.PubMedCrossRefGoogle Scholar
  15. 15.
    Martín MJ, La-Casa C, Alarcon-de-la-Lastra C, Cabeza J, Villegas I, Motilva V. Anti-oxidant mechanisms involved in gastroprotective effects of quercetin. Z Naturforsch 1998;53:82–88.Google Scholar
  16. 16.
    Lage AP, Godfroid E, Fauconnier A, Burette A, Butzler JP, Bollen A, et al. Diagnosis of Helicobacter pylori infection by PCR comparison with other invasive techniques and detection of Cag A gene in gastric biopsy specimen. J Clin Microbiol 1995;33:2752–2756.PubMedGoogle Scholar
  17. 17.
    Atherton JC, Cao P, Peek RM, Tummuru MKR, Blaser MJ, Cover TL. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. J Biol Chem 1995;270:17771–17777.PubMedCrossRefGoogle Scholar
  18. 18.
    Tummuru MK, Cover TL, Blasé MJ. Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun 1993;61:1799–1809.PubMedGoogle Scholar
  19. 19.
    Nourooz-Zadeh J, Tajaddini-Sarmadi J, Wolff SP. Measurement of plasma hydroperoxide concentrations by the ferrous oxidationxylenol orange assay in conjunction with triphenylphosphine. Anal Biochem 1994;220:403–409.PubMedCrossRefGoogle Scholar
  20. 20.
    Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–254.PubMedCrossRefGoogle Scholar
  21. 21.
    Williams D. Enzyme Histochemistry Chapter 22. In: Prophet EB, Mills Bob, Arrington JB, Sobin LS, editors. Laboratory methods in histotechnology. 2nd ed. Washington: American Registry of Pathology; 1994. p. 244–246.Google Scholar
  22. 22.
    Gray SF, Wyatt JI, Rathbone BJ. Simplified techniques for identifying Campylobacter pyloridis. J Clin Pathol 1986;39:1279.PubMedCrossRefGoogle Scholar
  23. 23.
    Aydin O, Egilmez R, Karabacak T, Kanik A. Interobserver variation in histopathological assessment of Helicobacter pylori gastritis. World J Gastroenterol 2003;9:2232–2235.PubMedGoogle Scholar
  24. 24.
    Kobayashi Y, Okazaki K, Murakami K. Adhesion of Helicobacter pylori to gastric epithelial cells in primary cultures obtained from stomachs of various animals. Infect Immun 1993;61:4058–4063.PubMedGoogle Scholar
  25. 25.
    Mähler M, Heidtmann W, Niewiesk S, Gruber A, Fossmark R, Beil W, et al. Experimental Helicobacter pylori infection induces antral-predominant, chronic active gastritis in hispid cotton rats (Sigmodon hispidus). Helicobacter 2005;10:332–344.PubMedCrossRefGoogle Scholar
  26. 26.
    Shin JE, Kim JM, Bae EA, Hyun YJ, Kim DH. In vitro inhibitory effect of flavonoids on growth, infection and vacuolation of Helicobacter pylori. Planta Med 2005;71:197–201.PubMedCrossRefGoogle Scholar
  27. 27.
    Konstantinopoulou M, Karioti A, Skaltsas S, Skaltsa H. Sesquiterpene lactones from Anthemis altissima and their anti-Helicobacter pylori activity. J Nat Prod 2003;66:699–702.PubMedCrossRefGoogle Scholar
  28. 28.
    Van Zaten SJ, Kolesnikow T, Leung V, O’Rourke JL, Lee A. Gastric transitional zones, areas where Helicobacter treatment fails: results of a treatment trial using the Sydney strain mouse model. Antimicrob. Agents Chemother 2003;47:2249–2255.CrossRefGoogle Scholar
  29. 29.
    Tombola F, Campello S, De Luca L, Ruggiero P, Del Giudice G, Papini E, et al. Plant polyphenols inhibit VacA, a toxin secreted by the gastric pathogen Helicobacter pylori. FEBS Lett 2003;543:184–189.PubMedCrossRefGoogle Scholar
  30. 30.
    Szabo I, Brutsche S, Tombola F, Moschioni M, Satín B, Telford JL, et al. Formation of anion-selective channels in the cell plasma membrane by the toxin VacA of Helicobacter pylori is required for its biological activity. EMBO J 1999;18:5517–5527.PubMedCrossRefGoogle Scholar
  31. 31.
    Xiao ZP, Shi DH, Li HQ, Zhang LN, Xu C, Zhu HL. Polyphenols based on isoflavones as inhibitors of Helicobacter pylori urease. Bioorg Med Chem 2007;15:3703–3710.PubMedCrossRefGoogle Scholar
  32. 32.
    Guo M, Perez C, Wei Y, Rapoza E, Su G, Bou-Abdallah F, Chasteen ND. Iron-binding properties of plant phenolics and cranberry’s bio-effects. Dalton Trans 2007;43:4951–4961.PubMedCrossRefGoogle Scholar
  33. 33.
    Bland MV, Salim I, Heinemann JA, Keenan JI. The action of bismuth against Helicobacter pylori mimics but is not caused by intracellular iron deprivation. Antimicrob Agents Chemother 2004;48:1983–1988.PubMedCrossRefGoogle Scholar
  34. 34.
    Suzuki M, Mori M, Miyayama A, Iwai N, Tsunematsu N, Oonuki M, et al. Enhancement of neutrophil infiltration in the corpus after failure of Helicobacter pylori eradication. J Clin Gastroenterol 1997;25:222–228.CrossRefGoogle Scholar
  35. 35.
    Ohkusa T, Fujiki K, Takashimizu I, Kumagai J, Tanizawa T, Eishi Y, et al. Improvement in atrophic gastritis and intestinal metaplasia in patients in whom Helicobacter pylori was eradicated. Ann Intern Med 2001;134:380–386.PubMedGoogle Scholar
  36. 36.
    Min YD, Choi CH, Bark H, Son HY, Park HH, Lee S, et al. Quercetin inhibits expression of inflammatory cytokines through attenuation of NF-kappaB and p38 MAPK in HMC-1 human mast cell line. Inflamm Res 2007;56:210–215.PubMedCrossRefGoogle Scholar
  37. 37.
    Ruiz PA, Braune A, Hölzlwimmer G, Quintanilla-Fend L, Haller D. Quercetin inhibits TNF-induced NF-kappaB transcription factor recruitment to proinflammatory gene promoters in murine intestinal epithelial cells. J Nutr 2007;137:1208–1215.PubMedGoogle Scholar
  38. 38.
    Shomer NH, Dangler CA, Whary MT, Fox JG. Experimental Helicobacter pylori infection induces antral gastritis and gastric mucosa-associated lymphoid tissue in guinea pigs. Infect Immun 1998;66:2614–2618.PubMedGoogle Scholar
  39. 39.
    Rijpkema SG, Durrani Z, Beavan G, Gibson JR, Luck J, Owen RJ, et al. Analysis of host responses of guinea pigs during Helicobacter pylori infection. FEMS Immunol Med Microbiol 2001;30:151–156.PubMedCrossRefGoogle Scholar
  40. 40.
    Moorchung N, Srivastava AN, Gupta NK, Malaviya AK, Achyut BR, Mittal B. The role of mast cells and eosinophils in chronic gastritis. Clin Exp Med 2006;6:107–114.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2008

Authors and Affiliations

  • Rodolfo González-Segovia
    • 1
  • J. Luis Quintanar
    • 2
  • Eva Salinas
    • 1
  • Rebeca Ceballos-Salazar
    • 1
  • Francisco Aviles-Jiménez
    • 3
  • Javier Torres-López
    • 3
  1. 1.Department of Microbiology, Centro de Ciencias Básicas, Universidad Autónoma de AguascalientesCiudad UniversitariaAguascalientes AgsMéxico
  2. 2.Department of Physiology and Pharmacology, Centro de Ciencias BásicasUniversidad Autónoma de AguascalientesAguascalientes AgsMéxico
  3. 3.Infectious Diseases Research Unit, Hospital de PediatriaCentro Médico Nacional SXXI, IMSSMéxico CityMéxico

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