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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 388, Issue 3, pp 305–317 | Cite as

Antiulcerogenic activity of Carica papaya seed in rats

  • Lorraine Aparecida Pinto
  • Kátia Wolff Cordeiro
  • Viviane Carrasco
  • Carlos Alexandre Carollo
  • Cláudia Andréa Lima Cardoso
  • Eliana Janet Sanjinez Argadoña
  • Karine de Cássia Freitas
Original Article

Abstract

The purpose of the present study was to evaluate the gastroprotective and healing effects of the methanolic extract of the seed of the papaya Carica papaya L. (MECP) in rats. Models of acute gastric ulcer induction by ethanol and indomethacin and of chronic ulcer by acetic acid were used. The gastric juice and mucus parameters were evaluated using the pylorus ligation model, and the involvement of sulfhydryl compounds (GSH) and nitric oxide in the gastroprotective effect was analyzed using the ethanol model. The toxicity was assessed through toxicity tests. No signs of toxicity were observed when the rats received a single dose of 2000 mg/kg of extract. The MECP in doses of 125, 250, and 500 mg/kg significantly reduced the gastric lesion with 56, 76, and 82 % inhibition, respectively, and a dose of 30 mg/kg lansoprazole showed 79 % inhibition in the ethanol model. MECP (125, 250, 500 mg/kg) and cimetidine (200 mg/kg) reduced the gastric lesion in the indomethacin model, with 62, 67, 81, and 85 % inhibition, respectively. The MECP (500 mg/kg) and cimetidine (200 mg/kg) treatments showed a reduction in ulcerative symptoms induced by acetic acid by 84 and 73 %, respectively. The antiulcerogenic activity seems to involve GSH because the inhibition dropped from 72 to 13 % in the presence of a GSH inhibitor. Moreover, the MECP showed systemic action, increasing the mucus production and decreasing gastric acidity. Treatments with MECP induce gastroprotection without signs of toxicity. This effect seems to involve sulfhydryl compounds, increased mucus, and reduced gastric acidity.

Keywords

Ulcer gastric Papaya Stomach Gastritis Rodents Medicinal plants 

Notes

Acknowledgments

We thank the National Counsel of Technological and Scientific Development (CNPq) for funding this research.

References

  1. Abdulla MA, Ahmed KAA, Al-Bayaty FH, Masood Y (2010) Gastroprotective effect of Phyllanthus niruri leaf extract against ethanol-induced gastric mucosal injury in rats. Afr J Pharm Pharmacol 4:226–230Google Scholar
  2. Adeneyea AA, Olagunjub JA (2009) Preliminary hypoglycemic and hypolipidemic activities of the aqueous seed extract of Carica papaya Linn. in Wistar rats. Biol Med J 1:1–10Google Scholar
  3. Afalobi IS, Marcus GD, Olanrewaju TO, Chizea V (2011) Biochemical effect of some food processing methods on the health promoting properties of under-utilized Carica papaya seed. J Nat Prod 4:17–24Google Scholar
  4. Agostini-Costa TS, Garruti DS, Lima L, Freire S, Abreu FAP, Feitosa T (1999) Avaliação de metodologias para determinação de taninos no suco de caju. B CEPPA 17:167–176Google Scholar
  5. Anaga AO, Onehi EV (2010) Antinociceptive and anti-inflammatory effects of the methanol seed extract of Carica papaya in mice and rats. Afr J Pharm Pharmacol 4:140–144Google Scholar
  6. Andrade SF, Antoniolli D, Comunello E, Cardoso LGV, Carvalho JCT, Bastos JK (2006) Antiulcerogenic activity of crude extract, fractions and populnoic acid isolated from Austroplenckia populnea (Celastraceae) Zeitschrift fur Naturforschung C. J Biosci 61:329–333Google Scholar
  7. Baker ME (1994) Licorice and enzymes other than 11β-hydroxysteroid dehydrogenase: an evolutionary perspective. Steroids 59:136–141CrossRefPubMedGoogle Scholar
  8. Barreiro EJ (2002) Estratégia de simplificação molecular no planejamento racional de fármacos: A descoberta de novos agente cardioativo. Quim Nova 25:1172–1180CrossRefGoogle Scholar
  9. Berté PE, Lopes JS, Comandulli NG, Rangel DW, Monache FD, Cechinel-Filho V, Niero R, Andrade SF (2014) Evaluation of the gastroprotective activity of the extracts, fractions, and pure compounds obtained from aerial parts of Rubus imperialis in different experimental models. Naunyn-Schmiedeberg’s Arch Pharmacol 387:313–319CrossRefGoogle Scholar
  10. Blackler R, Syer S, Bolla M, Ongini E, Wallace JL (2012) Gastrointestinal-sparing effects of novel NSAIDs in rats with compromised mucosal defence. Plos One 7:1–4CrossRefGoogle Scholar
  11. Boltin D, Halpern M, Levi Z, Vilkin A, Morgenstern S, Ho SB, Niv Y (2012) Gastric mucin expression in Helicobacter pylori-related, nonsteroidal anti-inflammatory drug-related and idiopathic ulcers. World J Gastroenterol 18:4597–4603CrossRefPubMedCentralPubMedGoogle Scholar
  12. Borrelli F, Izzo AA (2000) The plant kingdom as a source of anti-ulcer remedies. Phytochem Res 8:581–591Google Scholar
  13. Broadhurst RB, Jones WT (1978) Analysis of condensed tannins using acidified vanillin. J Sci Food Agric 29:788–794CrossRefGoogle Scholar
  14. Carlos IZ, Lopes FCM, Benzatti FP, Carli CBA, Marques MF, Jordão Junior CM, Rinaldo D, Calvo TR, Santos LC, Vilegas W (2005) Ação do extrato metanólico e etanólico de Davilla elliptica St. Hill. (Malpighiaceae) na resposta imune. Rev Bras Farmacogn 15:44–50CrossRefGoogle Scholar
  15. Carvalho CA, Fernandes KM, Matta SL, Silva MB, Oliveira LL, Fonseca CC (2011) Evaluation of antiulcerogenic activity of aqueous extract of Brassica oleracea var. capitata (cabbage) on Wistar rat gastric ulceration. Arq Gastroenterol 48:276–282PubMedGoogle Scholar
  16. Carvalho KI, Bonamin F, Santos RC, Périco LL, Beserra FP, Sousa DP, Filho JM, Rocha LR, Hiruma-Lima CA (2014) Geraniol-a flavoring agent with multifunctional effects in protecting the gastric and duodenal mucosa. Naunyn Schmiedebergs Arch Pharmacol 387:355–365CrossRefPubMedGoogle Scholar
  17. Chan FK, Leung WK (2002) Peptic-ulcer disease. Lancet 360:933–941CrossRefPubMedGoogle Scholar
  18. Cordeiro KW, Pinto LA, Formagio ASN, Andrade SF, Kassuya CAL, Freitas KC (2012) Antiulcerogenic effect of Croton urucurana baillon Bark. J Ethnopharmacol 143:331–337CrossRefGoogle Scholar
  19. Da Silva NLA, Miranda FAA, Da Conceição GM (2010) Triagem fitoquímica de plantas de cerrado, da área de proteção ambiental municipal do Inhamum. Scientia Plena 6:1–7Google Scholar
  20. Dinkova-Kostova AT, Kostov RV (2012) Glucosinolates and isothiocyanates in health and disease. Trends Mol Med 18:1–11CrossRefGoogle Scholar
  21. Djeridane A, Yousfi M, Nadjemi B, Boutassouna D, Stocker P, Vidal N (2006) Antioxidant activity of some Algerian medicinal plants extracts containing phenolic compounds. Food Chem 97:654–660CrossRefGoogle Scholar
  22. Food and Drug Administration (2005) Department of Health and Human Services. Center for Drug Evaluation and Research. Guidance for industry estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. Rockville, Maryland, USA Pharmacology and Toxicology Guidance for industry: estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteersGoogle Scholar
  23. Dugo L, Collin M, Cuzzocrea S, Thiemermann C (2004) 15d-prostaglandin J2 reduces multiple organ failure caused by wall-fragment of Gram-positive and Gram-negative bacteria. Eur J Pharmacol 498:295–301CrossRefPubMedGoogle Scholar
  24. Ezike AC, Akah PA, Okoli CO, Ezeuchenne NA, Ezeugwu S (2009) Carica papaya (paw-paw) unripe fruit may be beneficial in ulcer. J Med Food 6:1268–1273CrossRefGoogle Scholar
  25. Falcão HS, Leite JA, Filho JMB, Athayde-Filho PF, Chaves MCO, Moura MD, Ferreira AL, Almeida ABA, Souza-Brito ARM, Diniz MFFM, Batista LM (2012) Gastric and duodenal antiulcer activity of Alkaloids: a review. Molecules 13:3198–3223CrossRefGoogle Scholar
  26. Fenner R, Betti AH, Mentz LA, Rates SMK (2006) Plantas utilizadas na medicina popular brasileira com potencial atividade antifúngica. Braz J Pharm Sci 42:369–394CrossRefGoogle Scholar
  27. Glavin GB, Szabo S (1992) Experimental gastric mucosal injury: laboratory models reveal mechanisms of pathogenesis and new therapeutic strategies. Faseb J 3:825–831Google Scholar
  28. Hamman WO, Musa SA, Ikyembe DT, Umana UE, Adelaiye AB, Nok AJ, Ojo SA (2011) Chronic oral administration of ethanol extract of Carica papaya seeds does not affect the histology of the cauda epididymis of adult male Wistar rats. Asian J Med Sci 5:192–194Google Scholar
  29. Hayden LJ, Thomas G, West GB (1978) Inhibitors of gastric lesions in the rat. J Pharm Pharmacol 30:244–246CrossRefPubMedGoogle Scholar
  30. Indran M, Mahmood AA, Kuppusamy UR (2008) Protective effect of Carica papaya L leaf extract against alcohol induced acute gastric damage and blood oxidative stress in rats. West Indian Med J 57:323–326PubMedGoogle Scholar
  31. Jainu M, Devi CSS (2006) Antiulcerogenic and ulcer healing effects of Solanum nigrum (L.) on experimental ulcer models: possible mechanism for the inhibition of acid formation. J Ethnopharmacol 104:156–163CrossRefPubMedGoogle Scholar
  32. Khosla P, Karan RS, Bhargava VK (2004) Effect of garlic oil on ethanol induced gastric ulcers in rats. Phytochem Res 18:87–91Google Scholar
  33. Klein LC Jr, Gandolfi RB, Santin JR, Lemos M, Cechinel-Filho V, Andrade SF (2010) Antiulcerogenic activity of extract, fractions, and some compounds obtained from Polygala cyparissias St. Hillaire & Moquin (Polygalaceae). Naunyn-Schmiedeberg’s Arch Pharmacol 381:121–126CrossRefGoogle Scholar
  34. Klein LC Jr, Santina JR, Lemos M, Silveira ACO, Rocha JAR, Beber AP, Wagner TM, Bresolina TMB, Bella-Cruza A, Cechinel-Filhoa V, Andrade SF (2013) Role of gastric mucus secretion, oxinitrergic system and sulfhydryl groups on the gastroprotection elicited by Polygala cyparissias (Polygalaceae) in mice. J Pharm Pharmacol 65:797–776Google Scholar
  35. Lemos M, Santin JR, Júnior LC, Niero R, Andrade SF (2011) Gastroprotective activity of hydroalcoholic extract obtained from the leaves of Brassica oleracea var. Acephala DC in different animal models. J Ethnopharmacol 138:503–507CrossRefPubMedGoogle Scholar
  36. Lima GRM, Montenegro CA, Falcão HS, Jesus NZT, Cabral AGS, Gomes IF, Agra MF, Tavares JF, Batista LM (2012) Gastroprotective activity of the ethanolic extract and hexane phase of Combretum duarteanum Cambess. (Combretaceae). J Nat Med 1:1–11Google Scholar
  37. Lin JY, Tang CY (2007) Determination of total phenolic and flavonoid contents in selected fruits and vegetables, as well as their stimulatory effects on mouse splenocyte proliferation. Food Chem 101:140–147CrossRefGoogle Scholar
  38. Lohiya NK, Mishra PK, Pathak N, Manivannan B, Bhande SS, Panneerdoss S, Sriram S (2005) Efficacy trial on the purified compounds of the seeds of Carica papaya for male contraception in albino rat. Reprod Toxicol 20:135–148CrossRefPubMedGoogle Scholar
  39. Lucio EMRA, Rosalen PL, Sharapin N, Souza Brito ARM (2000) Avaliação toxicológica aguda e screening hipocrático da epiisopilosina, alcalóide secundário de Pilocarpus microphyllus Stapf. Rev Bras Farmacogn 1:23–35Google Scholar
  40. Malfertheiner P, Chan FK, Mccoll KE (2009) Peptic ulcer disease. Lancet 374:1449–1461CrossRefPubMedGoogle Scholar
  41. Matsuda H, Li Y, Yoshikawa M (1999) Roles of capsaicin-sensitive sensory nerves, endogenous nitric oxide, sulphydryls, and prostaglandins in gastroprotection by mormodin Ic, on oleanolic acid oligoglycoside, on ethanol-induced gastric mucosal lesion in rats. Life Sci 65:27–32CrossRefGoogle Scholar
  42. Matsuda H, Ochi M, Nagatomo A, Yoshikawa M (2007) Effects of allyl isothiocyanate from horseradish on several experimental gastric lesions in rats. Eur J Pharmacol 561:172–181CrossRefPubMedGoogle Scholar
  43. Mello JCP, Santos SC (2004) Taninos. In: Simões CMO, Schenkel EP, Gosmann G, Mello JCP, Mentz LA, Petrovick PR (eds) Farmacognosia: da planta ao medicamento, 6th. UFSC, Florianópolis, pp 615–656Google Scholar
  44. Mello VJ, Gomes MTR, Lemos FO, Delfino JL, Andrade SP, Lopes MTP, Salas CE (2008) The gastric ulcer protective and healing role of cysteine proteinases from Carica candamarcensis. Phytomedicine 15:237–244CrossRefPubMedGoogle Scholar
  45. Morimoto Y, Shimohara K, Oshima S, Sukamoto T (1991) Effects of the new anti-ulcer agent KB-5492 on experimental gastric mucosal lesions and gastric mucosal defensive factors, as compared to those of teprenone and cimetidine. Jpn J Pharmacol 57:495–505CrossRefPubMedGoogle Scholar
  46. Mota KSL, Dias GEN, Pinto MEF, Ferreira AL, Souza-Brito ARM, Hiruma-Lima CA, Barbosa-Filho JM, Batista LM (2009) Flavonoids with gastroprotective activity. Molecules 14:979–1012CrossRefPubMedGoogle Scholar
  47. Nguyen TT, Shaw PN, Parat MO, Hewavitharana AK (2012) Anticancer activity of Carica papaya: a review. Mol Nutr Food Res 57:153–164CrossRefPubMedGoogle Scholar
  48. O’Brien P, Carrasco-Pozo C, Speisky H (2006) Boldine and its antioxidant or health-promoting properties. Chem Biol Interact 159:1–17CrossRefPubMedGoogle Scholar
  49. O’Malley P (2003) Gastric ulcers and gerd: the new “plagues” of the 21st century update for the clinical nurse specialist. Clin Nurse Spec 17:286–289CrossRefPubMedGoogle Scholar
  50. OECD (2001) Guideline for testing of chemicals: acute oral toxicity-acute toxic class method 423: 1–14Google Scholar
  51. Okabe S, Amagase K (2005) An overview of acetic acid ulcer models the history and state of the art of peptic ulcer research. Biol Pharm Bull 8:1321–1341CrossRefGoogle Scholar
  52. Okewumi TA, Oyeyemi AW (2012) Gastro-protective activity of aqueous Carica papaya seed extract on ethanol induced gastric ulcer in male rats. Afr J Biotechnol 34:8612–8615Google Scholar
  53. Omar NAM, Abdullah N, Kuppusamy UR, Abdulla MA, Sabaratnam V (2011) Nutritional composition, antioxidant activities, and antiulcer potential of Lentinus squarrosulus (mont.) Mycelia extract”. Evid Based Complement Altern Med 1:1–8CrossRefGoogle Scholar
  54. Orsi PR, Bonamin F, Severi JA, Santos RC, Vilegas W, Hiruma-Lima CA, Di Stasi LC (2012) Hymenaea stigonocarpa Mart. ex Hayne: a Brazilian medicinal plant with gastric and duodenal anti-ulcer and antidiarrheal effects in experimental rodent models. J Ethnopharmacol 143:81–90CrossRefGoogle Scholar
  55. Polo CM, Moraes TM, Pellizzon CH, Marques MO, Rocha LRM, Hiruma–Lima CA (2012) Gastric ulcers in middle-aged rats: the healing effect of essential oil from Citrus aurantium L. (Rutaceae). Evid Based Complement Altern Med 1:1–8CrossRefGoogle Scholar
  56. Rahgozar M, Toroudi HRP, Bakhtiarian A, Djahanguiri B (2002) Diazoxide, a KATP channel opener, prevented ethanol-induced gastric ulceration in rats. Iran J Pharmacol Ther 1:5–7Google Scholar
  57. Reagan-Shaw S, Nihal M, Ahmad N (2007) Dose translation from animal to human studies revisited. FASEB J 22:659–661CrossRefPubMedGoogle Scholar
  58. Repetto MG, Llesuy SF (2002) Antioxidant properties of natural compounds used in popular medicine for gastric ulcers. Braz J Med Biol Res 5:523–534Google Scholar
  59. Sener G, Paskaloglu K, Anyaanoglu-Dulger G (2004) Protective effect of increasing doses of famotidine, omeprazole, lansoprazole, and melatonin against ethanol-induced gastric damage in rats. Indian J Pharmacol 36:171–174Google Scholar
  60. Shay H, Komarov SA, Fels SS, Marenze D, Grunstein M, Siplet H (1945) A simple method for the uniform production of gastric ulceration in the rat. Gastroenterol 5:43–61Google Scholar
  61. Sidahmed HM, Azizan AH, Mohan S, Abdulla MA, Abdelwahab SI, Taha MM, Hadi AH, Ketuly KA, Hashim NM, Loke MF, Vadivelu J (2013) Gastroprotective effect of desmosdumotin C isolated from Mitrella kentii against ethanol-induced gastric mucosal hemorrhage in rats: possible involvement of glutathione, heat-shock protein-70, sulfhydryl compounds, nitric oxide, and anti-Helicobacter pylori activity. BMC Complement Altern Med 13:1–183CrossRefGoogle Scholar
  62. Silva GG, Diniz RG, Silva ME (2007) Avaliação química do mamão papaia (Carica papaya Linn) Em diferentes estádios de maturação. Rev Capixaba Cien Tecnol 3:1–7Google Scholar
  63. Sumbul S, Ahmad MA, Mohd A, Mohd A (2011) Role of phenolic compounds in peptic ulcer: an overview. J Pharm Bioall Sci 3:361–367CrossRefGoogle Scholar
  64. Sun SB, Matsumoto T, Yamada H (1991) Effects of a polysaccharide fraction from the roots of Bupleurum folcatum L. on experimental gastric ulcer models in rats and mice. J Pharm Pharmacol 43:669–704CrossRefGoogle Scholar
  65. Tamma NV, Ashraf TN, Nagakrishna L, Sudhakar L, Challa S (2011) Evaluation of antinociceptive and anti-inflammatory effect of aqueous seed extract of Carica papaya Linn in albino rats. Int J Med Health Sci 2:305–310Google Scholar
  66. Tarnawski A (2000) Molecular mechanisms of ulcer healing. Drug News Perspect 13:158–168CrossRefPubMedGoogle Scholar
  67. Thorsen K, Soreide JA, Kvaløy JT, Glomsaker T, Soreide K (2013) Epidemiology of perforated peptic ulcer: age- and gender-adjusted analysis of incidence and mortality. World J Gastroenterol 19:347–354CrossRefPubMedCentralPubMedGoogle Scholar
  68. Toma W, Trigo JR, Paula ABC, Souza Brito ARM (2004) Preventive activity of pyrrolizidine alkaloids from Senecio brasiliensis (Asteraceae) on gastric and duodenal induced ulcer on mice and rats. J Ethnopharmacol 95:345–351CrossRefPubMedGoogle Scholar
  69. Vasconcelos PCP, Andreo MA, Vilegas W, Hiruma-Lima CA, Pellizzon CH (2010) Effect of Mouriri pusa tannins and flavonoids on prevention and treatment against experimental gastric ulcer. J Ethnopharmacol 131:146–153CrossRefPubMedGoogle Scholar
  70. Venturini T, Benchimol LR, Bertuol DA, Rosa MB, Meili L (2012) Estudo da secagem e extração de sementes de mamão (Carica papaya L.). Rev Eletr Gest Educ Tecnol Amb 5:950–959Google Scholar
  71. Yadava SK, Adhikarya B, Bandyopadhyaya SK, Chattopadhyay S (2013) Inhibition of TNF-α, and NF-κB and JNK pathways accounts for the prophylactic action of the natural phenolic, allylpyrocatechol against indomethacin gastropathy. Biochim Biophys Acta 1830:3776–3786CrossRefGoogle Scholar
  72. Yanaka A, Fahey JW, Fukumoto A, Nakayama M, Inoue S, Zhang S, Tauchi M, Suzuki H, Hyodo I, Yamamoto M (2009) Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and humans. Cancer Prev Res 4:353–360CrossRefGoogle Scholar
  73. Yuan Y, Padol IT, Hunt RH (2006) Peptic ulcer disease today. Nat Clin Pract Gastroenterol Hepatol 3:80–89CrossRefPubMedGoogle Scholar
  74. Zapata-Colindres JC, Zepeda-Gómez S, Montaño-Loza A, Vázquez-Ballesteros E, Villalobos JJ, Valdovinos-Andraca F (2006) The association of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs in peptic ulcer disease. Can J Gastroenterol 20:277–280PubMedCentralPubMedGoogle Scholar
  75. Zelickson MS, Bronder CM, Johnson BL, Camunas JA, De S, Rawlinson D, Von S, Stone HH, Taylor SM (2011) Helicobacter pylori is not the predominant etiology for peptic ulcers requiring operation. Am Surg 77:1054–1060PubMedGoogle Scholar
  76. Zhou K, Wang H, Mei W, Li X, Luo Y, Dai H (2011) Antioxidant activity of papaya seed extract. Molecules 16:6179–6192CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Lorraine Aparecida Pinto
    • 1
  • Kátia Wolff Cordeiro
    • 2
  • Viviane Carrasco
    • 1
  • Carlos Alexandre Carollo
    • 3
  • Cláudia Andréa Lima Cardoso
    • 4
  • Eliana Janet Sanjinez Argadoña
    • 5
  • Karine de Cássia Freitas
    • 6
    • 7
  1. 1.School of Health SciencesFederal University of Grande DouradosDouradosBrazil
  2. 2.School of MedicineFederal University of Mato Grosso do SulCampo GrandeBrazil
  3. 3.Department of Pharmacy and BiochemistryFederal University of Mato Grosso do SulCampo GrandeBrazil
  4. 4.Chemistry CenterState University of Mato Grosso do SulDouradosBrazil
  5. 5.School of EngineeringFederal University of Grande DouradosDouradosBrazil
  6. 6.Biological and Health Sciences CenterFederal University of Mato Grosso do SulCampo GrandeBrazil
  7. 7.Centro de Ciências Biológicas e da SaúdeUniversidade Federal do Mato Grosso do SulCampo GrandeBrazil

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