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Gastroprotective activity of carvacrol on experimentally induced gastric lesions in rodents

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Abstract

The present study aimed to investigate the gastroprotective activity of carvacrol, a monoterpene present in essential oils from several species of medicinal and aromatic plants, by using different models of acute gastric lesions in rodents and also evaluate possible mechanisms involved in this action. For this study, absolute ethanol-, acidified ethanol-, ischemia and reperfusion-, and nonsteroidal anti-inflammatory drug-induced models of gastric lesions in mice and rats were used. The roles of nonprotein sulfhydryl groups, catalase, nitric oxide (NO), ATP-sensitive potassium channels (KATP channels), and prostaglandins in carvacrol-induced gastroprotective effect were investigated. In addition, the effects of carvacrol on gastric secretion and mucus in pylorus-ligated rats were also determined. The results of the present study demonstrated that carvacrol promoted a marked gastroprotection in all models investigated, possibly mediated by endogenous prostaglandins, increase of mucus production, KATP channels opening, NO synthase activation, and antioxidant properties. These findings markedly substantiate further studies to investigate the therapeutic potential of carvacrol as an effective gastroprotective agent and its safety profile in medicinal use.

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References

  • Almeida RN, Navarro DS, Barbosa-Filho JM (2001) Plants with central analgesic activity. Phytomedicine 8:310–322

    Article  PubMed  CAS  Google Scholar 

  • Amaral JF, Silva MI, Neto MR, Neto PF, Moura BA, de Melo CT, de Araújo FL, de Sousa DP, de Vasconcelos PF, de Vasconcelos SM, de Sousa FC (2007) Antinociceptive effect of the monoterpene R-(+)-limonene in mice. Biol Pharm Bull 30:1217–1220

    Article  PubMed  Google Scholar 

  • Amaral MPM, Braga FAV, Passos FFB, Almeida FRC, Oliveira RCM, Carvalho AA, Chaves MH, Oliveira F (2009) Additional evidence for the anti-inflammatory properties of the essential oil of Protium heptaphyllum resin in mice and rats. Lat Am Pharm 28:775–82

    CAS  Google Scholar 

  • Argolo ACC, Sant'Ana AEG, Pletsch M, Coelho LCBB (2004) Antioxidant activity of leaf extracts from Bauhinia monandra. Biores Technol 95:229–233

    Article  CAS  Google Scholar 

  • Astudillo A, Hong E, Bye R, Navarrete A (2004) Antispasmodic activity of extracts and compounds of Acalypha phleoides cav. Phytother Res 18:102–106

    Article  PubMed  CAS  Google Scholar 

  • Avila JR, de la Lastra CA, Martin MJ, Motilva V, Luque I, Delgado D, Esteban J, Herrerias J (1996) Role of endogenous sulphydryls and neutrophil infiltration in the pathogenesis of gastric mucosal injury induced by piroxicam in rats. Inflamm Res 45:83–88

    Article  PubMed  CAS  Google Scholar 

  • Bandyopadhyay U, Biswas K, Chatterjee R, Bandyopadhyay D, Chattopadhyay I, Ganguly CK, Chakraborty T, Bhattacharya K, Banerjee RK (2002) Gastroprotective effect of Neem (Azadirachta indica) bark extract: possible involvement of H(+)–K(+)-ATPase inhibition and scavenging of hydroxyl radical. Life Sci 71:2845–2865

    Article  PubMed  CAS  Google Scholar 

  • Beers RF Jr, Sizer IW (1952) A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem 95:133–140

    Google Scholar 

  • Ben Arfa A, Combes S, Preziosi-Belloy L, Gontard N, Chalier P (2006) Antimicrobial activity of carvacrol related to its chemical structure. Lett Appl Microbiol 43:149–154

    Article  PubMed  CAS  Google Scholar 

  • Berenguer B, Trabadela C, Sánchez-Fidalgo S, Quílez A, Miño P, de la Puerta R, Martín-Calero MJ (2007) The aerial parts of Guazuma ulmifolia Lam. protect against NSAID-induced gastric lesions. J Ethnopharmacol 114:153–160

    Article  PubMed  CAS  Google Scholar 

  • Bhargava KP, Gupta MB, Tangri KK (1973) Mechanism of ulcerogenic activity of indomethacin and oxyphenbutazone. Eur J Pharmacol 22:191–195

    Article  PubMed  CAS  Google Scholar 

  • Brand-Williams W, Cuvelier ME, Berset C (1995) Use of a free radical method to evaluate antioxidant activity. LWT - Food Sci Technol 28:25–30

    Article  CAS  Google Scholar 

  • Canbek M, Uyanoglu M, Bayramoglu G, Senturk H, Erkasap N, Koken T, Uslu S, Demirustu C, Aral E, Husnu Can Baser K (2008) Effects of carvacrol on defects of ischemia–reperfusion in the rat liver. Phytomedicine 15:447–452

    Article  PubMed  CAS  Google Scholar 

  • Chan FK, Leung WK (2002) Peptic ulcer disease. The Lancet 360:933–941

    Article  Google Scholar 

  • Chi SC, Jun HW (1990) Anti-inflammatory activity of ketoprofen gel on carrageenan induced paw edema in rats. Int J Pharm 79:974–977

    CAS  Google Scholar 

  • Corne SJ, Morrissey SM, Woods RJ (1974) A method for the quantitative estimation of gastric barrier mucous. J Physiol 242:116–117

    Google Scholar 

  • Cunha FQ, Poole S, Lorenzetti BB, Ferreira SH (1992) The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia. Br J Pharmacol 107:660–664

    Article  PubMed  CAS  Google Scholar 

  • Cunha TM, Verri WA Jr, Silva JS, Poole S, Cunha FQ, Ferreira SH (2005) A cascade of cytokines mediates mechanical inflammatory hypernociception in mice. PNAS 102:1755–1760

    Article  PubMed  CAS  Google Scholar 

  • De Sousa DP, Gonçalves JC, Quintans-Júnior L, Cruz JS, Araújo DA, de Almeida RN (2006) Study of anticonvulsant effect of citronellol, a monoterpene alcohol, in rodents. Neurosci Lett 401:231–235

    Article  PubMed  Google Scholar 

  • Enomoto S, Asano R, Iwahori Y, Narui T, Okada Y, Singab AN, Okuyama T (2001) Hematological studies on black cumin oil from the seeds of Nigella sativa L. Biol Pharm Bull 24:307–310

    Article  PubMed  CAS  Google Scholar 

  • Fenaroli G (2002) Fenaroli’s handbook of flavor ingredients, 4th edn. CRC, Boca Raton

    Google Scholar 

  • Garcia ML, Hanner M, Hans-G K, Koch R, Schmalhofer W, Slaughter RS, Kaczorowski GJ (1997) Pharmacology of potassium channels. Adv Pharmacol 39:425–471

    Article  PubMed  CAS  Google Scholar 

  • Guimarães AG, Oliveira GF, Melo MS, Cavalcanti SC, Antoniolli AR, Bonjardim LR, Silva FA, Santos JP, Rocha RF, Moreira JC, Araújo AA, Gelain DP, Quintans-Júnior LJ (2010) Bioassay-guided evaluation of antioxidant and antinociceptive activities of carvacrol. Bas Clin Pharmacol Toxicol 107:949–957

    Article  Google Scholar 

  • Guimarães AG, Xavier MA, De Santana MT, Camargo EA, Santos CA, Brito FA, Barreto EO, Cavalcanti SC, Antoniolli AR, Oliveira RC, Quintans-Júnior LJ (2012) Carvacrol attenuates mechanical hypernociception and inflammatory response. Naunyn-Schmied Arch Pharmacol. doi:10.1007/s00210-011-0715-x

  • Halliwell B (1990) How to characterize a biological antioxidant. Free Radical Res Commun 9:1–32

    Article  CAS  Google Scholar 

  • Hiruma-Lima CA, Gracioso JS, Bighetti EJ, Grassi-Kassisse DM, Nunes DS, Brito AR (2002) Effect of essential oil obtained from Croton cajucara Benth. on gastric ulcer healing and protective factors of the gastric mucosa. Phytomedicine 9:523–529

    Article  PubMed  CAS  Google Scholar 

  • Hotta M, Nakata R, Katsukawa M, Hori K, Takahashi S, Inoue H (2010) Carvacrol, a component of thyme oil, activates PPAR alpha and gamma, and suppresses COX-2 expression. J Lipid Res 51:132–139

    Article  PubMed  Google Scholar 

  • Jenner PM, Hagan EC, Taylor JM, Cook EL, Fitzhugh OG (1964) Food flavourings and compounds of related structure. I. Acute oral toxicity. Food Cosm Toxicol 2:327–343

    Article  CAS  Google Scholar 

  • Kawai T, Joh T, Iwata F, Itoh M (1994) Gastric epithelial damage induced by local ischemia–reperfusion with or without exogenous acid. Am J Physiol 266:263–270

    Google Scholar 

  • Krimer N, Başer KHC, Tümen G (1995) Carvacrol rich plants in Turkey. Chem Nat Comp 31:37–42

    Article  Google Scholar 

  • Laine L, Takeuchi K, Tarnawski A (2008) Gastric mucosal defense and cytoprotection: bench to bedside. Gastroenterology 135:41–60

    Article  PubMed  CAS  Google Scholar 

  • Landa P, Kokoska L, Pribylova M, Vanek T, Marsik P (2009) In vitro anti-inflammatory activity of carvacrol: inhibitory effect on COX-2 catalyzed prostaglandin E2 biosynthesis. Arch Pharm Res 32:75–78

    Article  PubMed  CAS  Google Scholar 

  • Lemos TL, Matos FJA, Alencar JW, Craveiro AA, Clark AM, McChesney JD (1990) Antimicrobial activity of essential oil of Brazilian plants. Phytother Res 4:82–84

    Article  Google Scholar 

  • Lewis DA, Hanson PJ (1991) Anti-ulcer drugs of plant origin. In: Ellis GP, West GB (eds) Progress in medicinal chemistry, vol 28. Elsevier Science Publishers, Amsterdam, pp 201–231

    Google Scholar 

  • Li Y, Wang WP, Wang HY, Cho CH (2000) Intragastric administration of heparin enhances gastric ulcer healing through a nitric oxide dependent mechanism in rats. Eur J Pharmacol 399:205–214

    Article  PubMed  CAS  Google Scholar 

  • Maity P, Biswas K, Roy S, Banerjee RK, Bandyopadhyay U (2003) Smoking and the pathogenesis of gastroduodenal ulcer—recent mechanism update. Mol Cell Biochem 253:329–338

    Article  PubMed  CAS  Google Scholar 

  • Matsuda H, Li Y, Yoshikawa M (1999) Roles of capsaicin-sensitive sensory nerves, endogenous nitric oxide, sulphydryls, and prostaglandins in gastroprotection by mormodin Ic, an oleanolic acid oligoglycoside, on ethanol induced gastric mucosal lesion in rats. Life Sci 65:27–32

    Article  Google Scholar 

  • Matsunaga T, Hasegawa C, Kawasuji T, Suzuki H, Akiyama T, Sagioka T, Takahashi R, Tsukamoto H, Morikawa T (2000) Isolation of the antiulcer compound in essential oil from the leaves of Cryptomeria japonica. Biol Pharm Bull 23:595–598

    Article  PubMed  CAS  Google Scholar 

  • Mincis M, Chebli JMF, Khouri ST, Mincis R (1995) Etanol e o trato gastrointestinal. Arch Gastroenterol 32:131–139

    CAS  Google Scholar 

  • Olinda TM, Lemos TLG, Machado LL, Rao VS, Santos FA (2008) Quebrachitol-induced gastroprotection against acute gastric lesions: role of prostaglandins, nitric oxide and K+ATP channels. Phytomedicine 15:327–333

    Article  PubMed  Google Scholar 

  • Paula AC, Toma W, Gracioso JS, Hiruma-Lima CA, Carneiro EM, Souza Brito AR (2006) The gastroprotective effect of the essential oil of Croton cajucara is different in normal rats than in malnourished rats. B J Nutr 96:310–315

    Article  CAS  Google Scholar 

  • Peixoto-Neves D, Silva-Alves KS, Gomes MD, Lima FC, Lahlou S, Magalhães PJ, Ceccatto VM, Coelho-de-Souza AN, Leal-Cardoso JH (2010) Vasorelaxant effects of the monoterpenic phenol isomers, carvacrol and thymol, on rat isolated aorta. Fundam Clin Pharmacol 24:341–350

    Article  PubMed  CAS  Google Scholar 

  • Pongpiriyadacha Y, Matsuda H, Morikawa T, Asao Y, Yoshikawa M (2003) Protective effects of polygodial on gastric mucosal lesions induced by necrotizing agents in rats and the possible mechanisms of action. Biol Pharm Bull 26:651–657

    Article  PubMed  CAS  Google Scholar 

  • Rainsford KD (1998) An analysis from clinical–epidemiological data of the principal adverse events from the COX-2 selectives NSAID, nimesulide, with particular reference to hepatic injury. Inflammopharmacology 6:203–221

    Article  PubMed  CAS  Google Scholar 

  • Rao ChV, Ojha SK, Radhakrishnan K, Govindarajan R, Rastogi S, Mehrotra S, Pushpangadan P (2004) Antiulcer activity of Utleria salicifolia rhizome extract. J Ethnopharmacol 91:243–249

    Article  PubMed  Google Scholar 

  • Repetto MG, Llesuy SF (2002) Antioxidant properties of natural compounds used in popular medicine for gastric ulcers. Braz J Med Biol Res 35:523–534

    Article  PubMed  CAS  Google Scholar 

  • Robert A, Nezamis JE, Lancaster C, Hanchar AJ (1979) Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl and thermal injury. Gastroenterology 77:433–443

    PubMed  CAS  Google Scholar 

  • Rodríguez JA, Theoduloz C, Sánchez M, Yáñez T, Razmilic I, Schmeda-Hirschmann G (2005) Gastroprotective activity of a new semisynthetic solidagenone derivative in mice. J Pharm Pharmacol 57:265–271

    Article  PubMed  Google Scholar 

  • Samonina GE, Kopylova GN, Lukjanzeva GV, Zhuykova SE, Smirnova EA, German SV, Guseva AA (2004) Antiulcer effects of amylin: a review. Pathophysiology 11:1–6

    Article  PubMed  CAS  Google Scholar 

  • Sánchez M, Theoduloz C, Schmeda-Hirschmann G, Razmilic I, Yáñez T, Rodríguez JA (2006) Gastroprotective and ulcer-healing activity of oleanolic acid derivatives: in vitro–in vivo relationships. Life Sci 79:1349–1356

    Article  PubMed  Google Scholar 

  • Scholl I, Untersmayr E, Bakos N, Roth-Walter F, Gleiss A, Boltz-Nitulescu G, Scheiner O, Jensen-Jarolim E (2005) Antiulcer drugs promote oral sensitization and hypersensitivity to hazelnut allergens in BALB/c mice and humans. Amer J Clin Nut 81:154–160

    Google Scholar 

  • Shay H, Komarov SA, Fels SS, Meranze D, Gruenstein H, Siplet H (1945) A simple method for the uniform production of gastric ulceration in rat. Gastroenterology 5:43

    Google Scholar 

  • Silva MI, Moura BA, Neto MR, Tomé Ada R, Rocha NF, De Carvalho AM, Macêdo DS, Vasconcelos SM, De Sousa DP, Viana GS, De Sousa FC (2009) Gastroprotective activity of isopulegol on experimentally induced gastric lesions in mice: investigation of possible mechanisms of action. Naunyn-Schmied Arch Pharmacol 380:233–245

    Article  CAS  Google Scholar 

  • Soler-Rivas C, Espín JC, Wichers HJ (2000) An easy and fast test to compare total free radical scavenger capacity of foodstuffs. Phytochem Anal 11:1–9

    Article  Google Scholar 

  • Sun XB, Matsumoto T, Yamada H (1991) Effects of a polysaccharide fraction from the roots of Bupleurum folcatum L. on experimental gastric ulcer in rats and mice. J Pharm Pharmacol 43:699–704

    Article  PubMed  CAS  Google Scholar 

  • Szabo S, Trier JS, Frankel PW (1981) Sulfhydryl compounds may mediate gastric cytoprotection. Science 214:201–202

    Article  Google Scholar 

  • Szabo S, Kusstatscher S, Sakoulas G, Sandor Z, Vincze A, Jadus M (1995) Growth factors: new endogenous drugs for ulcer healing. Scand J Gastroenterol Suppl 210:15–18

    Article  PubMed  CAS  Google Scholar 

  • Szelenyi I, Thiemer K (1978) Distention ulcer as a model for testing of drugs for ulcerogenic side effects. Arch Toxicol 41:99–105

    Article  PubMed  CAS  Google Scholar 

  • Ueda S, Okada Y (1989) Acid secretagogues induce Ca++ mobilization coupled to K+ conductance activation in rat parietal cells in tissue culture. Biochem Biophys Acta 1012:254–260

    Article  PubMed  CAS  Google Scholar 

  • Van Den Broucke CO, Lemli JA (1982) Antispasmodic activity of Origanum compactum. Plant Med 45:188–190

    Article  Google Scholar 

  • Vonkeman HE, Klok RM, Postma MJ, Brouwers JR, Van de Laar MA (2007) Direct medical costs of serious gastrointestinal ulcers among users of NSAIDs. Drugs Aging 24:681–691

    Article  PubMed  Google Scholar 

  • Wallace JL (2001) Mechanisms of protection and healing: current knowledge and future research. Amer J Med 11:19S–23S

    Article  Google Scholar 

  • Wolfe MM, Sanche G (2000) Acid suppression: optimizing therapy for gastroduodenal ulcer healing, gastroesophageal reflux disease, and stress-related erosive syndrome. Gastroenterology 118:9–31

    Article  Google Scholar 

  • Zayachkivska OS, Konturek SJ, Drozdowicz D, Konturek PC, Brzozowski T, Ghegotsky MR (2005) Gastroprotective effects of flavonoids in plant extract. J Physiol Pharmacol 56:219–231

    PubMed  Google Scholar 

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Acknowledgments

We are thankful to UFPI (Federal University of Piauí, Brazil), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil), and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil) for the financial support. We also thank Prof. Daniel Dias Rufino Arcanjo, M.Sc. for the language proofreading and Mr. Carlos Alberto de Deus for the technical assistance. Additionally, there is no conflict of interest associated with this study.

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Authors and Affiliations

  1. Medicinal Plants Research Center, Federal University of Piauí, Av. Nossa Senhora de Fátima s/n, 64049-550, Teresina, Piauí, Brazil

    Irisdalva S. Oliveira, Francilene V. da Silva, Ana Flávia S. C. Viana, Maria do Carmo C. Martins, Paulo H. M. Nunes, Francisco de A. Oliveira & Rita de C. M. Oliveira

  2. Department of Physiology, Federal University of Sergipe, Aracaju, Sergipe, Brazil

    Márcio R. V. dos Santos & Lucindo J. Quintans-Júnior

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  1. Irisdalva S. Oliveira
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  2. Francilene V. da Silva
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  3. Ana Flávia S. C. Viana
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  4. Márcio R. V. dos Santos
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  6. Maria do Carmo C. Martins
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  8. Francisco de A. Oliveira
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  9. Rita de C. M. Oliveira
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Correspondence to Rita de C. M. Oliveira.

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Oliveira, I.S., da Silva, F.V., Viana, A.F.S.C. et al. Gastroprotective activity of carvacrol on experimentally induced gastric lesions in rodents. Naunyn-Schmiedeberg's Arch Pharmacol 385, 899–908 (2012). https://doi.org/10.1007/s00210-012-0771-x

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