Digestive Diseases and Sciences

, Volume 54, Issue 6, pp 1214–1221 | Cite as

The Effect of Hypericum perforatum (St. John’s Wort) on Experimental Colitis in Rat

  • Turhan Dost
  • Hakan Ozkayran
  • Filiz Gokalp
  • Cigdem Yenisey
  • Mustafa Birincioglu
Original Article
First Online:
Received:
Accepted:

Abstract

The aim of the present study was to investigate the effect of Hypericum perforatum (HP) on the inflammatory and immune response of colonic mucosa in rat with induced inflammatory bowel disease and that on various enzyme activities in blood and bowel tissue. Male Wistar albino rats were divided into three main groups: control, third day, and seventh day of colitis. Third-day and seventh-day groups were divided into four subgroups. Colitis was induced in all groups except the control group by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The colitis group received saline; treatment groups received HP extract (50, 150, and 300 mg/kg/day, respectively). Glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) activities in blood were measured. Catalase, myeloperoxidase (MPO), glutathione peroxidase (GSH-Px), glutathione reductase (GR), malondialdehyde, and nitric oxide (NO) activities were measured from tissue samples. Colonic damage was significantly reduced by HP extract. Macroscopic scoring of colonic damage significantly reduced in groups given HP extract compared with in the colitis group (P < 0.001). Blood catalase levels were reduced in the HP (150 mg/kg/day) compared with the colitis group (P < 0.01). Blood GSH levels significantly increased in groups treated with HP compared with control (P < 0.001) on the third and seventh day. Tissue GR levels reduced in the colitis and HP (50 mg/kg/day) groups compared with control (P < 0.05). Tissue MPO activity increased in the colitis and treatment groups compared with control (P < 0.007). GSH-Px levels increased in the colitis group compared with control at day 3 (P = 0.006). HP has a protective effect on TNBS-induced inflammatory bowel disease (IBD), probably due to an anti-inflammatory and antioxidant mechanism.

Keywords

TNBS Antioxidant system Hypericum perforatum (St. John’s wort) Inflammatory bowel disease 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This work was supported by a grant TPF-05010 from Adnan Menderes University Research Foundation. We are appreciative of Indena S.p.A. (Italy) for Hypericum perforatum extract.

References

  1. 1.
    Jurjus AR, Khoury NN, Reimund JM. Animal models of inflammatory bowel disease. J Pharmacol Toxicol Methods. 2004;50:81–92. doi: 10.1016/j.vascn.2003.12.002.PubMedCrossRefGoogle Scholar
  2. 2.
    Araki Y, Sugihara H, Hattori T. The free radical scavengers edaravone and tempol suppress experimental dextran sulfate sodium-induced colitis in mice. Int J Mol Med. 2006;17:331–334.PubMedGoogle Scholar
  3. 3.
    El-Sherbiny DA, Khalifa AE, Attia AS, et al. Hypericum perforatum extract demonstrates antioxidant properties against elevated rat brain oxidative status induced by amnestic dose of scopolamine. Pharmacol Biochem Behav. 2003;76:525–533. doi: 10.1016/j.pbb.2003.09.014.PubMedCrossRefGoogle Scholar
  4. 4.
    Dryden GW Jr, Deaciuc I, Arteel G, et al. Clinical implications of oxidative stress and antioxidant therapy. Curr Gastroenterol Rep. 2005;7:308–316. doi: 10.1007/s11894-005-0024-y.PubMedCrossRefGoogle Scholar
  5. 5.
    Conforti F, Statti GA, Tundis R, et al. Antioxidant activity of methanolic extract of Hypericum triquetrifolium Turra aerial part. Fitoterapia. 2002;73:479–483. doi: 10.1016/S0367-326X(02)00162-4.PubMedCrossRefGoogle Scholar
  6. 6.
    Benedi J, Arroyo R, Romero C, et al. Antioxidant properties and protective effects of a standardized extract of Hypericum perforatum on hydrogen peroxide-induced oxidative damage in PC12 cells. Life Sci. 2004;75:1263–1276. doi: 10.1016/j.lfs.2004.05.001.PubMedCrossRefGoogle Scholar
  7. 7.
    Couladis M, Baziou P, Verykokidou E, et al. Antioxidant activity of polyphenols from Hypericum triquetrifolium Turra. Phytother Res. 2002;16:769–770. doi: 10.1002/ptr.1062.PubMedCrossRefGoogle Scholar
  8. 8.
    Lawvere S, Mahoney MC. St. John’s wort. Am Fam Physician. 2005;72:2249–2254.PubMedGoogle Scholar
  9. 9.
    Miller AL. St. John’s Wort (Hypericum perforatum): clinical effects on depression and other conditions. Altern Med Rev. 1998;3:18–26.PubMedGoogle Scholar
  10. 10.
    Ozturk B, Apaydin S, Goldeli E, et al. Hypericum triquetrifolium Turra. Extract exhibits antiinflammatory activity in the rat. J Ethnopharmacol. 2002;80:207–209. doi: 10.1016/S0378-8741(02)00044-2.PubMedCrossRefGoogle Scholar
  11. 11.
    Hosseinzadeh H, Karimi GR, Rakhshanizadeh M. Anticonvulsant effect of Hypericum perforatum: role of nitric oxide. J Ethnopharmacol. 2005;98:207–208. doi: 10.1016/j.jep.2004.12.007.PubMedCrossRefGoogle Scholar
  12. 12.
    Viana AF, Heckler AP, Fenner R, et al. Antinociceptive activity of Hypericum caprifoliatum and Hypericum polyanthemum (Guttiferae). Braz J Med Biol Res. 2003;36:631–634.PubMedGoogle Scholar
  13. 13.
    Lavagna SM, Secci D, Chimenti P, et al. Efficacy of Hypericum and Calendula oils in the epithelial reconstruction of surgical wounds in childbirth with caesarean section. Farmaco. 2001;56:451–453. doi: 10.1016/S0014-827X(01)01060-6.PubMedCrossRefGoogle Scholar
  14. 14.
    Millar AD, Rampton DS, Chander CL, et al. Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis. Gut. 1996;39:407–415. doi: 10.1136/gut.39.3.407.PubMedCrossRefGoogle Scholar
  15. 15.
    Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351–358. doi: 10.1016/0003-2697(79)90738-3.PubMedCrossRefGoogle Scholar
  16. 16.
    Tietze F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem. 1969;27:502–522. doi: 10.1016/0003-2697(69)90064-5.PubMedCrossRefGoogle Scholar
  17. 17.
    Aebi H. Catalase. In: Bergmeyer HU, ed. Methods of Enzymatic Analysis. New York: Academic; 1974:673–677.Google Scholar
  18. 18.
    Dogan AL, Dogan A, Canpinar H, et al. Effect of fludarabine on leukocyte functions. Chemotherapy. 2004;50:283–288. doi: 10.1159/000082627.PubMedCrossRefGoogle Scholar
  19. 19.
    Kakkar R, Mantha SV, Radhi J, et al. Increased oxidative stress in rat liver and pancreas during progression of streptozotocin-induced diabetes. Clin Sci (Lond). 1998;94:623–632.Google Scholar
  20. 20.
    Racker E. Glutathione reductase (liver and yeast). In: Colowick SP, Kaplan NO, eds. Methods in Enzymology. New York: Academic; 1995:722–729.Google Scholar
  21. 21.
    Navarro-Gonzalvez JA, Garcia-Benayas C, Arenas J. Semiautomated measurement of nitrate in biological fluids. Clin Chem. 1998;44:679–681.PubMedGoogle Scholar
  22. 22.
    Morris GP, Beck PL, Herridge MS, et al. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology. 1989;96:795–803.PubMedGoogle Scholar
  23. 23.
    Zhou Q, Caudle RM, Price DD, et al. Selective up-regulation of NMDA-NR1 receptor expression in myenteric plexus after TNBS induced colitis in rats. Mol Pain. 2006;2:3.PubMedCrossRefGoogle Scholar
  24. 24.
    Cetinkaya A, Bulbuloglu E, Kurutas EB, et al. Beneficial effects of N-acetylcysteine on acetic acid-induced colitis in rats. Tohoku J Exp Med. 2005;206:131–139. doi: 10.1620/tjem.206.131.PubMedCrossRefGoogle Scholar
  25. 25.
    Cetinkaya A, Bulbuloglu E, Kantarceken B, et al. Effects of L-carnitine on oxidant/antioxidant status in acetic acid-induced colitis. Dig Dis Sci. 2006;51:488–494. doi: 10.1007/s10620-006-3160-9.PubMedCrossRefGoogle Scholar
  26. 26.
    Krawisz JE, Sharon P, Stenson WF. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology. 1984;87:1344–1350.PubMedGoogle Scholar
  27. 27.
    Sekizuka E, Grisham MB, Li MA, et al. Inflammation-induced intestinal hyperemia in the rat: role of neutrophils. Gastroenterology. 1988;95:1528–1534.PubMedGoogle Scholar
  28. 28.
    Deniz M, Cetinel S, Kurtel H. Blood flow alterations in TNBS-induced colitis: role of endothelin receptors. Inflamm Res. 2004;53:329–336. doi: 10.1007/s00011-004-1266-0.PubMedCrossRefGoogle Scholar
  29. 29.
    Kruidenier L, Kuiper I, Van Duijn W, et al. Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease. J Pathol. 2003;201:17–27. doi: 10.1002/path.1408.PubMedCrossRefGoogle Scholar
  30. 30.
    Mei Q, Xu JM, Xiang L, et al. Change of nitric oxide in experimental colitis and its inhibition by melatonin in vivo and in vitro. Postgrad Med J. 2005;81:667–672. doi: 10.1136/pgmj.2004.030817.PubMedCrossRefGoogle Scholar
  31. 31.
    Necefli A, Tulumoglu B, Giris M, et al. The effect of melatonin on TNBS-induced colitis. Dig Dis Sci. 2006;51:1538–1545. doi: 10.1007/s10620-005-9047-3.PubMedCrossRefGoogle Scholar
  32. 32.
    Raso GM, Pacilio M, Di Carlo G, et al. In-vivo and in-vitro anti-inflammatory effect of Echinacea purpurea and Hypericum perforatum. J Pharm Pharmacol. 2002;54:1379–1383. doi: 10.1211/002235702760345464.PubMedCrossRefGoogle Scholar
  33. 33.
    Albert D, Zundorf I, Dingermann T, et al. Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase. Biochem Pharmacol. 2002;64:1767–1775. doi: 10.1016/S0006-2952(02)01387-4.PubMedCrossRefGoogle Scholar
  34. 34.
    Bezakova L, Psenak M, Kartnig T. Effect of dianthrones and their precursors from Hypericum perforatum L. on lipoxygenase activity. Pharmazie. 1999;54:711.PubMedGoogle Scholar
  35. 35.
    Hammer KD, Hillwig ML, Solco AK, et al. Inhibition of prostaglandin E(2) production by anti-inflammatory Hypericum perforatum extracts and constituents in RAW264.7 mouse macrophage cells. J Agric Food Chem. 2007;55:7323–7331. doi: 10.1021/jf0710074.PubMedCrossRefGoogle Scholar
  36. 36.
    Ozturk N, Korkmaz S, Ozturk Y. Wound-healing activity of St. John’s Wort (Hypericum perforatum L.) on chicken embryonic fibroblasts. J Ethnopharmacol. 2007;111:33–39. doi: 10.1016/j.jep.2006.10.029.PubMedCrossRefGoogle Scholar
  37. 37.
    Liu SP, Dong WG, Wu DF, et al. Protective effect of angelica sinensis polysaccharide on experimental immunological colon injury in rats. World J Gastroenterol. 2003;9:2786–2790.PubMedGoogle Scholar
  38. 38.
    Pavlick KP, Laroux FS, Fuseler J, et al. Role of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease. Free Radic Biol Med. 2002;33:311–322. doi: 10.1016/S0891-5849(02)00853-5.PubMedCrossRefGoogle Scholar
  39. 39.
    Sanchez-Reus MI, Gomez Del Rio MA, Iglesias I, et al. Standardized Hypericum perforatum reduces oxidative stress and increases gene expression of antioxidant enzymes on rotenone-exposed rats. Neuropharmacology. 2007;52:606–616.Google Scholar
  40. 40.
    Gianetti J, Pedrinelli R, Petrucci R, et al. Inverse association between carotid intima-media thickness and the antioxidant lycopene in atherosclerosis. Am Heart J. 2002;143:467–474. doi: 10.1067/mhj.2002.120776.PubMedCrossRefGoogle Scholar
  41. 41.
    El Midaoui A, de Champlain J. Prevention of hypertension, insulin resistance, and oxidative stress by alpha-lipoic acid. Hypertension. 2002;39:303–307. doi: 10.1161/hy0202.104345.PubMedCrossRefGoogle Scholar
  42. 42.
    Yakobson MG, Antonov AR, Golovatyuk AV, et al. Iron content and parameters of blood antioxidant activity in rats with hereditary arterial hypertension during experimental myocardial infarction. Bull Exp Biol Med. 2001;132:1041–1044.PubMedGoogle Scholar
  43. 43.
    Percy ME. Catalase: an old enzyme with a new role? Can J Biochem Cell Biol. 1984;62:1006–1014.PubMedCrossRefGoogle Scholar
  44. 44.
    Giris M, Erbil Y, Dogru-Abbasoglu S, et al. The effect of heme oxygenase-1 induction by glutamine on TNBS-induced colitis: the effect of glutamine on TNBS colitis. Int J Colorectal Dis. 2007;22:591–599.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Turhan Dost
    • 1
  • Hakan Ozkayran
    • 1
  • Filiz Gokalp
    • 1
  • Cigdem Yenisey
    • 2
  • Mustafa Birincioglu
    • 1
  1. 1.Department of Pharmacology, Medical FacultyAdnan Menderes UniversityAydinTurkey
  2. 2.Department of Biochemistry, Medical FacultyAdnan Menderes UniversityAydinTurkey

Personalised recommendations