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Journal of Natural Medicines

, Volume 60, Issue 3, pp 198–205 | Cite as

Effects of curcumin on reflux esophagitis in rats

  • Sirima Mahattanadul
  • Nisaudah Radenahmad
  • Narubodee Phadoongsombut
  • Thitima Chuchom
  • Pharkphoom Panichayupakaranant
  • Shingo Yano
  • Wantana Reanmongkol
Original Paper

Abstract

The preventive effect of curcumin, a compound isolated from the rhizome of Curcuma longa, on experimental reflux esophagitis in rats was investigated in order to validate its potential therapeutic use for gastroesophageal reflux disease. Curcumin (20 mg/kg, i.d.), the antioxidative agent dimethyl sulfoxide (DMSO) (1 ml/kg, i.p.) or the proton pump inhibitor lansoprazole (1 mg/kg, i.d.) inhibited the formation of acute acid reflux esophagitis by 52.5, 61.5 and 70.9% respectively. Curcumin alone was not effective in preventing chronic acid reflux esophagitis, but the combination of curcumin and DMSO reduced the mortality rate and the severity of the esophagitis ulcer index to the same extent (56.5%) as did the lansoprazole (53.9%). Intraduodenal administration of curcumin also markedly prevented the formation of acute mixed reflux esophagitis, together with reducing the incidence or the severity of neutrophil infiltration, when compared to a control group. In contrast, lansoprazole tended to increase the severity of all histopathological changes, when compared to either the control or the curcumin-treated group. Aminoguanidine, a specific inducible nitric oxide synthase inhibitor, had no preventive effect against both types of acute reflux esophagitis models, and increased the mortality in the chronic acid reflux esophagitis model. From these results, it is indicated that curcumin can effectively prevent acute reflux esophagitis formation. Although curcumin is less potent than lansoprazole in inhibiting acid reflux esophagitis, it is superior to lansoprazole in inhibiting mixed reflux esophagitis. The antiulcerogenic mechanisms are considered to be closely associated with its antioxidant nature and antiinflammatory property.

Keywords

Curcumin Acid reflux esophagitis Mixed reflux esophagitis Preventive action 

Notes

Acknowledgments

The authors are grateful to Graduate School, Prince of Songkla University and Ministry of University Affairs, Thailand for financial support of this work. We thank Dr. Brian Hodgson for correction and improvement of the manuscript.

References

  1. 1.
    Kauer WKH, Peters JH, DeMeester TR, Ireland AP, Bremner CG, Hagen JA (1995) Mixed reflux of gastric and duodenal juices is more harmful to the esophagus than gastric juice alone. The need for surgical therapy re-emphasized. Ann Surg 222:525–533CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Lillemoe KD, Johnson LF, Harmon JW (1983) Alkaline esophagitis: a comparison of the ability of components of gastroduodenal contents to injure the rabbit esophagus. Gastroenterology 85:621–628PubMedGoogle Scholar
  3. 3.
    Wetscher GJ, Hinder RA, Bagchi D, Hinder PR, Bagchi M, Perdikis G, McGinn T (1995) Reflux esophagitis in humans is mediated by oxygen derived free radicals. Am J Surg 170:552–557CrossRefPubMedGoogle Scholar
  4. 4.
    Wetscher GJ, Perdikis G, Kretchmar DH, Stinson RG, Bagchi D, Redmond EJ, Adrian TE, Hinder RA (1995) Esophagitis in Sprague-Dawley rats is mediated by free radicals. Dig Dis Sci 40:1297–1305CrossRefPubMedGoogle Scholar
  5. 5.
    Wetscher GJ, Hinder PR, Bagchi D, Perdikis G, Redmond EJ, Glaser K, Adrian TE, Hinder RA (1995) Free radical scavengers prevent reflux esophagitis in rats. Dig Dis Sci 40:1292–1296CrossRefPubMedGoogle Scholar
  6. 6.
    Oh TY, Lee JS, Ahn BO, Cho H, Kim WB, Kim YB, Surh YJ, Cho SW, Lee KM, Hahm KB (2001) Oxidative stress is more important than acid in the pathogenesis of reflux oesophagitis in rats. Gut 49:364–371CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Ammon HPT, Safayhi H, Mack T, Sabieraj J (1993) Mechanism of anti-inflammatory actions of curcumin and boswellic acids. J Ethnopharmacol 38:113–119CrossRefPubMedGoogle Scholar
  8. 8.
    Chan MMY, Huang HI, Fenton MR, Fong D (1998) In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties. Biochem Pharmacol 55:1955–1962CrossRefPubMedGoogle Scholar
  9. 9.
    Jobin C, Bradham CA, Russo MP, Juma B, Narula AS, Brenner DA, Sartor R (1999) Curcumin blocks cytokine mediated NF-κ-B activation and proinflammatory gene expression by inhibiting inhibitory factor I-κ-B kinase activity. J Immunol 163:3474–3483PubMedGoogle Scholar
  10. 10.
    Sreejayan N, Rao MN (1997) Nitric oxide scavenging by curcuminoids. J Pharm Pharmacol 49:105–107CrossRefPubMedGoogle Scholar
  11. 11.
    Das KC, Das CK (2002) Curcumin (diferuloylmethane), a singlet oxygen (1O2) quencher. Biochem Biophys Res Commun 295:62–66CrossRefPubMedGoogle Scholar
  12. 12.
    Sinha M, Mukherjee BP, Mukherjee B, Sikdar S, Dasgupta SR (1975) Study of the mechanism of action of curcumin: an antiulcer agent. Ind J Pharmacol 7:98Google Scholar
  13. 13.
    Kosuge T, Ishida H, Yamazaki H (1985) Studies on active substances in the herbs used for Oketsu (“Stagnant blood”) in Chinese medicine III. On the anticoagulative principles in Curcuma rhizome. Chem Pharm Bull (Tokyo) 33:1499–1502CrossRefGoogle Scholar
  14. 14.
    Roughley PJ, Whiting DA (1973) Experiments in the biosynthesis of curcumin. J Chem Soc 40:3741–3746Google Scholar
  15. 15.
    Nakamura K, Ozawa Y, Furuta Y, Miyazaki H (1982) Effects of sodium polyacrylate (PANa) on acute esophagitis by gastric juice in rats. Jpn J Pharmacol 32:445–456CrossRefPubMedGoogle Scholar
  16. 16.
    Anson ML (1938) The estimation of pepsin, trypsin, papain and cathepepsin with hemoglobin. J Gen Physiol 22:79–89CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Omura N, Kashiwagi H, Chen G, Suzuki Y, Yano F, Aoki T (1999) Establishment of surgically induced chronic acid reflux esophagitis in rats. Scand J Gastroenterol 34:948–953CrossRefPubMedGoogle Scholar
  18. 18.
    Satoh H, Inatomi N, Nagaya H, Inada I, Nohara A, Nakamura N, Maki Y (1989) Antisecretory and antiulcer activities of a novel proton pump inhibitor AG-1749 in dogs and rats. J Pharm Exp Ther 248:806–815Google Scholar
  19. 19.
    Chandranath SI, Bastaki SMA, Singh J (2002) A comparative study on the activity of lansoprazole, omeprazole and PD-136450 on acidified ethanol- and indomethacin—induced gastric lesions in the rat. Clin Exp Pharm Physiol 29:173–180CrossRefGoogle Scholar
  20. 20.
    Biswas K, Bandyopadhyay, Chattopadhyay I, Varadaraj A, Ali E, Banerjee RK (2003) A novel antioxidant and antiapoptotic role of omeprazole to block gastric ulcer through scavenging of hydroxyl radical. J Biol Chem 278:10993–11001CrossRefPubMedGoogle Scholar
  21. 21.
    Shimizu S, Simon RP, Graham SH (1997) Dimethylsulfoxide (DMSO) treatment reduces infarction volume after permanent focal cerebral ischemia in rats. Neurosci Lett 239:125–127CrossRefPubMedGoogle Scholar
  22. 22.
    Devasena T, Rajasekaran KN, Gunasekaran G, Viswanathan P, Menon VP (2003) Anticarcinogenic effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione a curcumin analog on DMH-induced colon cancer model. Pharmacol Res 47:133–140CrossRefPubMedGoogle Scholar
  23. 23.
    Wood DC, Wood J (1975) Pharmacologic and biochemical considerations of dimethyl sulfoxide. Ann NY Acad Sci 243:7–19CrossRefPubMedGoogle Scholar
  24. 24.
    Chang CK, Llanes S, Schumer W (1999) Inhibitory effect of dimethyl sulfoxide on nuclear factor-κ-B activation and intercellular adhesion molecule 1 gene expression in septic rats. J Surg Res 82:294–299CrossRefPubMedGoogle Scholar
  25. 25.
    Kawachi S, Cockrell A, Laroux FS, Gray L, Granger DN, Van Der Heyde HC, Grisham MB (1999) Role of inducible nitric oxide synthase in the regulation of VCAM-1 expression in gut inflammation. Am J Physiol 277:G572–G576CrossRefPubMedGoogle Scholar
  26. 26.
    McCafferty DM, Mudgett JS, Swain MG, Kubes P (1997) Inducible nitric oxide synthase plays a critical role in resolving intestinal inflammation. Gastroenterology 112:1022–1027CrossRefPubMedGoogle Scholar
  27. 27.
    Stein HS, Barlow AP, DeMeester TR, Hinder RA (1992) Complication of gastroesophageal reflux disease. Role of the lower esophageal sphincter, esophageal acid and acid/alkaline exposure, and duodenogastric reflux. Ann Surg 216:35–43CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Lee JS, Oh TY, Ahn BO, Cho H, Kim WB, Kim YB, Surh YJ, Kim HJ, Hahm KB (2001) Involvement of oxidative stress in experimentally induced reflux esophagitis and Barrett’s esophagus: clue for the chemoprevention of esophageal carcinoma by antioxidants. Mutat Res 480–481:189–200CrossRefPubMedGoogle Scholar
  29. 29.
    Tomatsuri N, Yoshida N, Takayama T, Yamaguchi T, Takagi T, Handa O, Ishikawa T, Matsumoto N, Ochiai J, Naito Y, Yoshikawa T (2001) Role of neutrophils and cytokines in esophagitis induced by reflux of gastro-duodenal contents. Ulcer Res 28:85–87Google Scholar
  30. 30.
    Vaezi MF, Singh S, Richter JE (1995) Role of acid and duodenogastric reflux in esophageal mucosal injury: a review of animal and human studies. Gastroenterology 108:1897–1907CrossRefPubMedGoogle Scholar
  31. 31.
    Krahenbuhl S, Talos C, Fischer S, Reichen J (1994) Toxicity of bile acids on the electron transport chain of isolated rat liver mitochondria. Hepatology 19:471–479PubMedGoogle Scholar
  32. 32.
    Bernstein H, Payne CM, Bernstein C, Schneider J, Beard SE, Crowley CL (1999) Activation of the promoters of genes associated with DNA damage, oxidative stress, ER stress and protein malfolding by the bile salt, deoxycholate. Toxicol Lett 108:37–46CrossRefPubMedGoogle Scholar
  33. 33.
    Furihata C, Takezawa R, Matrushima T, Tatematsu M (1987) Potential tumor-promoting activity of bile acids in rat glandular stomach. Jpn J Cancer Res 78:32–39PubMedGoogle Scholar
  34. 34.
    Zhang F, Subbaramaiah K, Altorki N, Dannenberg AJ (1998) Dihydroxy bile acids activate the transcription of cyclooxygenase-2. J Biol Chem 273:2424–2428CrossRefPubMedGoogle Scholar
  35. 35.
    Salo JA, Lehto VP, Kivilaakso E (1983) Morphological alterations in experimental esophagitis. Dig Dis Sci 28:440–448CrossRefPubMedGoogle Scholar
  36. 36.
    Deters M, Siegers C, Hansel W, Schneider KP, Hennighausen G (2000) Influence of curcumin on cyclosporin-induced reduction of biliary bilirubin and cholesterol excretion and on biliary excretion of cyclosporin and its metabolites. Planta Med 66:429–434CrossRefPubMedGoogle Scholar
  37. 37.
    Deters M, Klabunde T, Meyer H, Resch K, Kaever V (2002) Effects of curcumin on cyclosporine-induced cholestasis and hypercholesterolemia and on cyclosporine metabolism in the rat. Planta Med 69:337–343CrossRefGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer 2006

Authors and Affiliations

  • Sirima Mahattanadul
    • 1
  • Nisaudah Radenahmad
    • 2
  • Narubodee Phadoongsombut
    • 3
  • Thitima Chuchom
    • 3
  • Pharkphoom Panichayupakaranant
    • 4
  • Shingo Yano
    • 5
  • Wantana Reanmongkol
    • 1
  1. 1.Department of Clinical Pharmacy, Faculty of Pharmaceutical SciencesPrince of Songkla UniversityHat YaiThailand
  2. 2.Department of Anatomy, Faculty of SciencePrince of Songkla UniversityHat YaiThailand
  3. 3.Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical SciencesPrince of Songkla UniversityHat YaiThailand
  4. 4.Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical SciencesPrince of Songkla UniversityHat YaiThailand
  5. 5.Department of Molecular Pharmacology and Pharmacotherapeutics, Graduate School of Pharmaceutical SciencesChiba UniversityChuo-kuJapan

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