Advertisement

Journal of Natural Medicines

, Volume 67, Issue 1, pp 143–151 | Cite as

Protective effect of Chresta martii extract against indomethacin-induced gastric lesions in mice

  • A. A. R. SilvaEmail author
  • M. M. Bezerra
  • H. V. Chaves
  • K. M. A. Pereira
  • J. A. Aguiar
  • V. P. T. Pinto
  • C. Abbet
  • C. A. Simões-Pires
  • E. S. Franco
  • A. T. Henriques
  • K. Hostettmann
  • M. B. S. Maia
Original Paper

Abstract

Chresta martii (Asteraceae) is a plant found in the Xingó region (semi-arid area) in Northeastearn Brazil, and is recognized by the local population as a traditional herb used to treat gastric diseases. This is the first report of the chemical composition, acute toxicity, and gastroprotective effect in mice of the hydroalcoholic extract (HAE) from the aerial parts (leaves and flowers) of Chresta martii. Animals received HAE doses from 10 to 2000 mg/kg, i.p. or 50 to 3000 mg/kg, p.o.) and were observed over 48 h for toxicity signs and mortality; sub-chronic toxicity was evaluated through 14 days treatment with once-daily HAE doses (400 mg/kg, p.o.). The gastroprotective effect of HAE was demonstrated on the indomethacin-induced gastric ulcer model after the administration of extracts. Data comparison of ulcer index averages between saline and HAE (100 or 400 mg/kg, p.o.) groups showed significant (P < 0.01) inhibition (71.73 and 76.72 %, respectively) of indomethacin-induced gastric lesions. Histological analyses showed significant (P < 0.05) inhibition of leukocyte migration in HAE-treated groups. A fingerprint of the HAE obtained by HPLC/UV/MS analysis showed major peaks characteristic of sesquiterpene lactones. Compound 1 was isolated and elucidated as a new natural product. Its capacity to prevent leukocyte chemotaxis was demonstrated in vitro, corroborating the pharmacological effects observed for C. martii HAE.

Keywords

Chresta martii Asteraceae Sesquiterpene lactones Gastric ulcer 

Notes

Acknowledgments

This work was supported by Conselho Nacional de Desenvolvimento Científico e tecnológico (CNPq), Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP), Programa Rede Nordeste de Biotecnologia (RENORBIO) and the Swiss National Science Foundation (Grant no. 200010-100083 to K. Hostettmann).

References

  1. 1.
    Wang YR, Richter JE, Dempsey DT (2010) Trends and outcomes of hospitalizations for peptic ulcer disease in the United States, 1993 to 2006. Ann Surg 251:51–58PubMedCrossRefGoogle Scholar
  2. 2.
    Barocelli E, Chiavarini M, Ballabeni V, Barlocco D, Vianello P, Dal Piaz V, Impicciatore M (1997) Study of the antisecretory and antiulcer mechanisms of a new indenopirydazinone derivative in rats. Pharmacol Res 35:487–492PubMedCrossRefGoogle Scholar
  3. 3.
    Toma W, Trigo JR, Paula ACB, Brito ARMS (2004) Preventive activity of pyrrolizidine alkaloids from Senecio brasiliensis (Asteraceae) on gastric and duodenal induced ulcer on mice and rats. J Ethnopharmacol 95:345–351PubMedCrossRefGoogle Scholar
  4. 4.
    Robinson H (1980) Notes on the Lychnophorine genera Chresta and Eremanthus. Phytologia 45:89–100Google Scholar
  5. 5.
    Agra MF, Silva KN, Basilio IJLD, Freitas PF, Barbosa-Filho JM (2008) Survey of medicinal plants used in the region Northeast of Brazil. Braz J Pharmacog 18:472–508Google Scholar
  6. 6.
    Almeida CFCBR, de Amorim ELC, Albuquerque UP, Maia MBS (2006) Medicinal plants popularly used in the Xingo region—a semi-arid location in Northeastern Brazil. J Ethnobiol Ethnomed 2:1–7CrossRefGoogle Scholar
  7. 7.
    Almeida CFCBR, Silva TC, Amorim ELC, Maia MBS, Albuquerque UP (2005) Life strategy and chemical composition as predictors of the selection of medicinal plants from the caatinga (Northeast Brazil). J Arid Environ 62:127–142CrossRefGoogle Scholar
  8. 8.
    Roque N, Gonçalves JM, Dematteis M (2008) A new species of the Brazilian genus Chresta (Asteraceae, Vernonieae) from Bahia. Bot J Linnean Soc 157:587–590CrossRefGoogle Scholar
  9. 9.
    Miller LC, Tainter ML (1944) Estimation of the ED50 and its error by means of logarithmic-probit graph paper. Proc Soc Exp Biol Med 57:261–264Google Scholar
  10. 10.
    Szabo S, Trier JS, Brown A, Schnoor J (1985) Early vascular injury and increased vascular permeability in gastric mucosal injury caused by ethanol in the rat. Gastroenterology 88:228–236PubMedGoogle Scholar
  11. 11.
    Boyden S (1962) The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leukocytes. J Exp Med 15:433–466Google Scholar
  12. 12.
    Zigmond SH, Hirsch JH (1973) Leukocyte locomotion and chemotaxis. New methods for evaluation and demonstration of a cell-derived chemotactic factor. J Exp Med 137:387–410PubMedCrossRefGoogle Scholar
  13. 13.
    Ramirez MR, Apel MA, Raseira MCB, Zuanazzi JÂS, Henriques AT (2011) Polyphenol content and evaluation of antichemotactic, antiedematogenic and antioxidant activities of Rubus sp. cultivars. J Food Biochem 35:1389–1397CrossRefGoogle Scholar
  14. 14.
    Glasl S, Presser A, Gunbilig D, Werner I, Narantuya S, Haslinger E, Jurenitsch J, Kubelka W (2001) Highly hydroxylated guaianolides of Achillea asiatica and Middle European Achillea species. Phytochemistry 58:1189–1194PubMedCrossRefGoogle Scholar
  15. 15.
    Drotman RB, Lawhorn GT (1978) Serum enzymes as indicators of chemical induced liver damage. Drug Chem Toxicol 1:163–171PubMedCrossRefGoogle Scholar
  16. 16.
    Diniz MFFM, Medeiros IA, Santos HB, Oliveira KM, Vasconcelos THC, Aguiar FB, Toscano MG, Ribeiro EAN (2006) Haematological and biochemical parameter standardization of Swiss mice and Wistar rats. Rev Bras Ciências da Saúde 10(2):171–176Google Scholar
  17. 17.
    Mazzaccara C, Labruna G, Cito G, Scarfò M, Felice M, Pastore L, Sacchetti L (2008) Age-related reference intervals of the main biochemical and hematological parameters in C57BL/6J, 129SV/EV and C3H/HeJ mouse strains. PLoS ONE 3(11):e3772PubMedCrossRefGoogle Scholar
  18. 18.
    Boone L, Meyer D, Cusick P, Ennulat D, Bolliger AP, Everds N, Meador V, Elliott G, Honor D, Bounous D, Jordan H (2005) Selection and interpretation of clinical pathology indicators of hepatic injury in preclinical studies. Vet Clin Pathol 34(3):182–188PubMedCrossRefGoogle Scholar
  19. 19.
    Musumba C, Pritchard DM, Pirmohamed M (2009) Review article: cellular and molecular mechanisms of NSAID-induced peptic ulcers. Aliment Pharmacol Ther 30:517–531PubMedCrossRefGoogle Scholar
  20. 20.
    Wallace JL (2008) Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn’t the stomach digest itself? Physiol Rev 88:1547–1565PubMedCrossRefGoogle Scholar
  21. 21.
    Chandranath SI, Bastaki SMA, Singh J (2002) A comparative study on the activity of lansoprazole, omprazole and PD-136450 on acidified ethanol- and indomethacin-induced gastric lesions in the rat. Clin Exp Pharmacol Physiol 29:173–180PubMedCrossRefGoogle Scholar
  22. 22.
    Ferreira SH, Moncada S, Vane JR (1973) Some effects of inhibiting endogenous prostaglandin formation on the responses of the cat spleen. Braz J Pharmacol 47:48–58CrossRefGoogle Scholar
  23. 23.
    Suleyman H, Albayrak A, Bilici M, Cadirci E, Halici Z (2010) Different mechanisms in formation and prevention of indomethacin-induced gastric ulcers. Inflammation 33:224–234PubMedCrossRefGoogle Scholar
  24. 24.
    Wallace JL (2001) Mechanisms of protection and healing: current knowledge and future research. Am J Med 110:19S–23SPubMedCrossRefGoogle Scholar
  25. 25.
    Lutnicki K, Szpringer E, Czerny K, Ledwozyw A (2001) Effects of ethanol and arachidonic acid pathway inhibitors on the effectiveness of gastric mucosa cytoprotection. Folia Morphol (Warsz) 60:47–56Google Scholar
  26. 26.
    Souza M, Mota J, Oliveira R, Cunha F (2008) Gastric damage induced by different doses of indomethacin in rats is variably affected by inhibiting iNOS or leukocyte infiltration. Inflamm Res 57:28–33PubMedCrossRefGoogle Scholar
  27. 27.
    Chattopadhyay I, Bandyopadhyay U, Biswas K, Maity P, Banerjee RK (2006) Indomethacin inactivates gastric peroxidase to induce reactive-oxygen-mediated gastric mucosal injury and curcumin protects it by preventing peroxidase inactivation and scavenging reactive oxygen. Free Radic Biol Med 40:1397–1408PubMedCrossRefGoogle Scholar
  28. 28.
    Hanan E-A (2010) Coenzyme Q10: A novel gastroprotective effect via modulation of vascular permeability, prostaglandin E2, nitric oxide and redox status in indomethacin-induced gastric ulcer model. Eur J Pharmacol 649:314–319CrossRefGoogle Scholar
  29. 29.
    Szabo S, Nagy L, Plebani M (1992) Glutathione, protein sulfhydryls and cysteine proteases in gastric mucosal injury and protection. Clin Chim Acta 206:95–105PubMedCrossRefGoogle Scholar
  30. 30.
    Baggio CH, Freitas CS, Rieck L, Marques MCA (2003) Gastroprotective effects of a crude extract of Baccharis illinita DC in rats. Pharmacol Res 47:93–98PubMedCrossRefGoogle Scholar
  31. 31.
    Dias LFT, Melo ES, Hernandes LS, Bacchi EM (2009) Antiulcerogenic and antioxidant activities of Baccharis trimera (Less) DC (Asteraceae). Braz J Pharmacogn 19:309–314Google Scholar
  32. 32.
    Silverio MS, Sousa OV, Del-Vechio-Vieira G, Miranda MA, Matheus FC, Kaplan MAC (2008) Pharmacological properties of the ethanol extract from Eremanthus erythropappus (DC.) McLeisch. Braz J Pharmacog 18:430–435Google Scholar
  33. 33.
    Repetto MG, Llesuy SF (2002) Antioxidant properties of natural compounds used in popular medicine for gastric ulcers. Braz J Med Biol Res 35:523–534PubMedCrossRefGoogle Scholar
  34. 34.
    Giordano OS, Guerreiro E, Pestchanker MJ, Guzman J, Pastor D, Guardia T (1990) The gastric cytoprotective effect of several sesquiterpene lactones. J Nat Prod 53:803–809PubMedCrossRefGoogle Scholar
  35. 35.
    Giordano OS, Pestchanker MJ, Guerreiro E, Saad JR, Enriz RD, Rodriguez AM, Juregui EA, Guzmn J, Mara AO, Wendel GH (1992) Structure-activity relationship in the gastric cytoprotective effect of several sesquiterpene lactones. J Med Chem 35:2452–2458PubMedCrossRefGoogle Scholar
  36. 36.
    Gürbüz I, Yesilada E (2007) Evaluation of the anti-ulcerogenic effect of sesquiterpene lactones from Centaurea solstitialis L. ssp. solstitialis by using various in vivo and biochemical techniques. J Ethnopharmacol 112:284–291PubMedCrossRefGoogle Scholar
  37. 37.
    Heinrich M, Robles M, West JE, Ortiz de Montellano BR, Rodriguez E (1998) Ethnopharmacology of Mexican Asteraceae (Compositae). Annu Rev Pharmacol Toxicol 38:539–565PubMedCrossRefGoogle Scholar
  38. 38.
    Tournier H, Schinella G, de Balsa EM, Buschiazzo H, Manez S, Mordujovich de Buschiazzo P (1999) Effect of the chloroform extract of Tanacetum vulgare and one of its active principles, parthenolide, on experimental gastric ulcer in rats. J Pharm Pharmacol 51:215–219PubMedCrossRefGoogle Scholar
  39. 39.
    Yesilada E, Gürbüz I, Bedir E, Tatli I, Khan IA (2004) Isolation of anti-ulcerogenic sesquiterpene lactones from Centaurea solstitialis L. ssp. solstitialis through bioassay-guided fractionation procedures in rats. J Ethnopharmacol 95:213–219PubMedCrossRefGoogle Scholar
  40. 40.
    Guardia T, Guzman JA (1994) Mucus synthesis and sulfhydryl groups in cytoprotection mediated by dehydroleucodine, a sesquiterpene lactone. J Nat Prod 57(4):507–509PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer 2012

Authors and Affiliations

  • A. A. R. Silva
    • 1
    Email author
  • M. M. Bezerra
    • 1
  • H. V. Chaves
    • 1
  • K. M. A. Pereira
    • 1
  • J. A. Aguiar
    • 1
  • V. P. T. Pinto
    • 2
  • C. Abbet
    • 3
  • C. A. Simões-Pires
    • 3
  • E. S. Franco
    • 4
  • A. T. Henriques
    • 5
  • K. Hostettmann
    • 3
  • M. B. S. Maia
    • 4
  1. 1.Laboratory of Pharmacology of Sobral (LaFS)Federal University of Ceará BrazilSobralBrazil
  2. 2.Laboratory of Biochemistry of Sobral, Master of Biotechnology Degree ProgramFederal University of CearáSobralBrazil
  3. 3.School of Pharmaceutical SciencesUniversity of Geneva, University of LausanneGenevaSwitzerland
  4. 4.Laboratory of Pharmacology of Bioactive Products, Department of Physiology and PharmacologyFederal University of PernambucoRecifeBrazil
  5. 5.Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de FarmáciaUFRGSPorto AlegreBrazil

Personalised recommendations