Skip to main content

Geraniol—a flavoring agent with multifunctional effects in protecting the gastric and duodenal mucosa

Naunyn-Schmiedeberg's Archives of Pharmacology volume 387, pages 355–365 (2014)Cite this article

Abstract

Geraniol is an acyclic monoterpene alcohol commonly used as a flavoring agent. The present study was undertaken to investigate antiulcerogenic effects of geraniol and to determine the possible mechanisms involved in this action. In the model of the ethanol-induced ulcer, treatment of rats with geraniol by oral route significantly inhibited gastric lesions by 70 % (7.50 mg/kg) to 99 % (200 mg/kg). Analysis of the gastric tissue of rats treated with geraniol (7.50 mg/kg) revealed that total glutathione content levels (GSH) increased and levels of myeloperoxidase (MPO) decreased in the gastric mucosa. Oral treatment with geraniol significantly decreased the number of ulcerative lesions induced by ischemia/reperfusion injury by 71 % and the duodenal ulcers induced by cysteamine by 68 %. The action of geraniol was mediated by the activation of defensive mucosa-protective factors such as the nitric oxide (NO) pathway, endogenous prostaglandins, increased mucus production, increased sulfhydryl compounds, antioxidant properties and the stimulation of calcitonin gene-related peptide (CGRP) release through the activation of transient receptor potential vanilloid (TRPV). The multifaceted gastroprotective mechanisms of geraniol represent a promising option for the treatment of gastric and duodenal mucosa injury.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  • Abdallah DM, El-Abhar HS, Abdel-Aziz DH (2009) TEMPOL, a membrane permeable radical scavenger, attenuates gastric mucosal damage induced by ischemia–reperfusion: a key role for superoxide anion. Eur J Pharmacol 603:93–97

    PubMed  Article  CAS  Google Scholar 

  • Allen A, Flemstrom G (2005) Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin. Am J Physiol Cell 288:1–19

    Google Scholar 

  • Anderson M (1985) Determination of glutathione disulfide in biological samples. Met Enzymol 113:548–555

    Article  CAS  Google Scholar 

  • Bakkali F, Averbeck S, Averbeck D, Idaomar M (2007) Biological effects of essential oils—a review. Food Chem Toxicol 46:446–475

    PubMed  Article  CAS  Google Scholar 

  • Besouw M, Masereeuw R, Van Den Heuvel L, Levtchenko E (2013) Cysteamine: an old drug with new potential. Drug Discov Today 18(15-16):785–92. doi: 10.1016/j.drudis.2013.02.003

    Google Scholar 

  • Cardozo MT, de Conti A, Ong TP, Scolastici C, Purgatto E, Horst MA, Bassoli BK, Moreno FS (2011) Chemopreventive effects of β-ionone and geraniol during rat hepatocarcinogenesis promotion: distinct actions on cell proliferation, apoptosis, HMGCoA reductase, and RhoA. J Nutr Biochem 22:130–135

    PubMed  Article  CAS  Google Scholar 

  • Carnesecchi S, Bras-Gonçalves R, Bradaia A, Zeisel M, Gossé F, Poupon MF, Raul F (2004) Geraniol, a component of plant essential oils, modulates DNA synthesis and potentiates 5-fluorouracil efficacy on human colon tumor xenografts. Cancer Lett 215:53–59

    PubMed  Article  CAS  Google Scholar 

  • Crowell PL (1999) Prevention and therapy of cancer by dietary monoterpenes. J Nutr 129:775S–778S

    PubMed  CAS  Google Scholar 

  • Garner A (1986) Future opportunities for drug therapy in peptic ulcer disease. Scand J Gastroenterol 125:203–210

    Article  CAS  Google Scholar 

  • Jeon JH, Lee CH, Lee HS (2009) Food protective effect of geraniol and its congeners against stored food mites. J Food Prot 72:1468–1471

    PubMed  CAS  Google Scholar 

  • Ji CX, Fan DS, Li W, Guo L, Xu ZL, Liang RM, Zhang JJ (2012) Evaluation of the anti-ulcerogenic activity of the antidepressants duloxetine, amitriptyline, fluoxetine and mirtazapine in different models of experimental gastric ulcer in rats. Eur J Pharmacol 691:46–51

    PubMed  Article  CAS  Google Scholar 

  • Khomenko T, Kolodney J, Pinto JT, McLaren GD, Deng X, Chen L, Tolstanova G, Paunovic B, Krasnikov BF, Hoa N, Cooper AJ, Szabo S (2012) New mechanistic explanation for the localization of ulcers in the rat duodenum: role of iron and selective uptake of cysteamine. Arch Biochem Biophys 525:60–70

    PubMed  Article  CAS  Google Scholar 

  • Kim H, Kim KH (2001) Role of nitric oxide and mucus in ischemia/reperfusion-induced gastric mucosal injury in rats. Pharmacology 62:200–207

    PubMed  Article  CAS  Google Scholar 

  • Krawisz JE, Sharon P, Stenson WF (1984) Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in the rat and hamster model. Gastroenterology 87:1344–1350

    PubMed  CAS  Google Scholar 

  • La Casa C, Villegas I, Alacrón de La Lastra C, Motilva V, Calero MJM (2000) Evidence for protective and antioxidant properties of rutin, a natural flavone, against ethanol induced gastric lesions. J Ethnopharmacol 71:45–53

    PubMed  Article  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  • Li NS, Luo XJ, Dai Z, Liu B, Zhang YS, Yang ZC, Peng J (2012) Beneficial effects of capsiate on ethanol-induced mucosal injury in rats are related to stimulation of calcitonin gene-related peptide release. Planta Med 78:24–30

    PubMed  Article  CAS  Google Scholar 

  • Luo XJ, Liu B, Dai Z, Yang ZC, Peng J (2013) Stimulation of calcitonin gene-related peptide release through targeting capsaicin receptor: a potential strategy for gastric mucosal protection. Dig Dis Sci 58:320–325

    PubMed  CAS  Google Scholar 

  • Madankumar A, Jayakumar S, Gokuladhas K, Rajan B, Raghunandhakumar S, Asokkumar S, Devaki T (2013) Geraniol modulates tongue and hepatic phase I and phase II conjugation activities and may contribute directly to the chemopreventive activity against experimental oral carcinogenesis. Eur J Pharmacol 705:148–155

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  • Muthuraman A, Ramesh M, Chauhan A (2011) Mitochondrial dependent apoptosis: ameliorative effect of flunarizine on ischemia–reperfusion of celiac artery-induced gastric lesions in the rat. Dig Dis Sci 56:2244–2251

    PubMed  Article  CAS  Google Scholar 

  • Naito Y, Yoshikawa T, Matsuyama K, Yagi N, Arai M, Nakamura Y, Kaneko T, Yoshida N, Kondo M (1998) Neutrophils, lipid peroxidation, and nitric oxide in gastric reperfusion injury in rats. Free Radic Biol Med 24:494–502

    PubMed  Article  CAS  Google Scholar 

  • Natale G, Lazzeri G, Lubrano V, Colucci R, Vassalle C, Fornai M, Blandizzi C, Del Tacca M (2004) Mechanisms of gastroprotection by lansoprazole pretreatment against experimentally induced injury in rats: role of mucosal oxidative damage and sulfhydryl compounds. Toxicol Appl Pharmacol 195:62–72

    PubMed  Article  CAS  Google Scholar 

  • Olfert ED, Cross BM, McWilliam AA (1993) Guide to the care and use of experimental animals. Canadian Council on Animal Care, Ottawa, Ontario, pp 1–13

    Google Scholar 

  • Oliveira IS, da Silva FV, Viana AF, dos Santos MR, Quintans-Júnior LJ, Martins MC, Nunes PH, Oliveira FA, Oliveira RC (2012) Gastroprotective activity of carvacrol on experimentally induced gastric lesions in rodents. N Schmied Arch Pharmacol 385:899–908

    Article  CAS  Google Scholar 

  • Phillips L, Toledo AH, Lopez-Neblina F, Anaya-Prado R, Toledo-Pereyra LH (2009) Nitric oxide mechanism of protection in ischemia and reperfusion injury. J Invest Surg 22:46–55

    PubMed  Article  Google Scholar 

  • Pongpiriyadacha Y, Matsuda H, Yoshikava 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

    PubMed  Article  CAS  Google Scholar 

  • Proença Cunha A (2005) Farmacognosia e Fitoquímica. Colouste F (ed) Gulbenkian Lisboa, Portugal

  • Rafatullah S, Tariq M, Al-Yahya MA, Mossa JS, Ageel AM (1990) Evaluation of tumeric (Curcuma longa) for gastric and duodenal antiulcer activity in rats. J Ethnopharmacol 29:25–34

    PubMed  Article  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 77:433–440

    PubMed  CAS  Google Scholar 

  • Shay H, Komarov SA, Fels SS, Meranze D, Gruenstein M, Siplet H (1945) A simple method for the uniform production of gastric ulceration in the rat. Gastroenterology 5:43–61

    Google Scholar 

  • Silva FV, Guimarães AG, Silva ER, Sousa-Neto BP, Machado FD, Quintans-Júnior LJ, Arcanjo DD, Oliveira FA, Oliveira RC (2012) Anti-inflammatory and anti-ulcer activities of carvacrol, a monoterpene present in the essential oil of oregano. J Med Food 15:984–991

    PubMed  Article  CAS  Google Scholar 

  • Silva MIG, Moura BA, Neto MRA, Tomé AR, Rocha NFM, Carvalho AMR, Macêdo DS, Vasconcelos SMM, Sousa DP, Viana GSB, Sousa CF (2009) Gastroprotective activity of isopulegol on experimentally induced gastric lesions in mice: investigation of possible mechanisms of action. Naunyn Schmiedeberg’s Arch Pharmacol 380:233–245

    Article  CAS  Google Scholar 

  • Siqueira BPJ, Menezes CT, Silva JP, Sousa DP, Batista JS (2012) Antiulcer effects of epoxy-carvone. Rev Bras Farmacog 22:144–149

    Article  CAS  Google Scholar 

  • Souza R, Cardoso M, Menezes C, Silva J, De Sousa D, Batista J (2011) Gastroprotective activity of α-terpineol in two experimental models of gastric ulcer in rats. Daru 19:277–281

    PubMed Central  PubMed  CAS  Google Scholar 

  • Szabo S (1987) Mechanisms of mucosal injury in the stomach and duodenum: time-sequence analysis of morphologic, functional, biochemical and histochemical studies. Scand J Gastroenterol 22:21–28

    Article  Google Scholar 

  • Szabo S, Nagy L, Plebani M (1992) Glutathione, protein sulfhydryls and cysteine proteases in gastric mucosal injury and protection. Clin Chim Acta 206:95–105

    PubMed  Article  CAS  Google Scholar 

  • Szallasi A (2006) Small molecule vanilloid TRPV1 receptor antagonist approaching drug status: can they live up to the expectations? Naunyn Schmiedeberg’s Arch Pharmacol 373:273–286

    Article  CAS  Google Scholar 

  • Takeuchi K, Kita K, Hayashi S, Aihara E (2011) Regulatory mechanism of duodenal bicarbonate secretion: roles of endogenous prostaglandins and nitric oxide. Pharmacol Ther 130:59–70

    PubMed  Article  CAS  Google Scholar 

  • Tarnawski AS, Ahluwalia A, Jones MK (2012) The mechanisms of gastric mucosal injury: focus on microvascular endothelium as a key target. Curr Med Chem 19:4–15

    PubMed  Article  CAS  Google Scholar 

  • Tiwari M, Kakkar P (2009) Plant derived antioxidants—geraniol and camphene protect rat alveolar macrophages against t-BHP induced oxidative stress. Toxicol in Vitro 23:295–301

    PubMed  Article  CAS  Google Scholar 

  • Tytgat GN (2011) Etiopathogenetic principles and peptic ulcer disease classification. Dig Dis 29:454–458

    PubMed  Article  CAS  Google Scholar 

  • Ueda S, Yoshikawa T, Takahashi S, Ichikawa H, Yasuda M, Oyamada H, Tanigawa T, Sugino S, Kondo M (1989) Role of free radicals and lipid peroxidation in gastric mucosal injury induced by ischemia–reperfusion in rats. Scand J Gastroenterol 162:55–58

    Article  CAS  Google Scholar 

  • Vinothkumar V, Manoharan S, Sindhu G, Nirmal MR, Vetrichelvi V (2012) Geraniol modulates cell proliferation, apoptosis, inflammation, and angiogenesis during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Mol Cell Biochem 369:17–25

    PubMed  Article  CAS  Google Scholar 

  • Wang SL, Wu-Wang CY, Slomiany A, Slomiany BL (1994) Effect of acute ethanol treatment on epidermal growth factor receptor in the rat stomach. Alcohol 11:11–15

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors are thankful to FAPESP (Fundação de Amparo a Pesquisa do Estado de São Paulo) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnologico) for financial support.

Conflict of interest

The authors declare no conflict of interest.

Author information

Affiliations

  1. Departamento de Fisiologia, Instituto de Biociências, Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Botucatu, São Paulo, Brazil

    Katharinne Ingrid Moraes de Carvalho, Flavia Bonamin, Raquel Cássia dos Santos, Larissa Lucena Périco, Fernando Pereira Beserra, Lucia Regina Machado da Rocha & Clelia Akiko Hiruma-Lima

  2. Centro de Biotecnologia, Universidade Federal da Paraíba, 58051-970, João Pessoa, Paraíba, Brazil

    Damião Pergentino de Sousa & José Maria Barbosa Filho

Authors
  1. Katharinne Ingrid Moraes de Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Flavia Bonamin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raquel Cássia dos Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Larissa Lucena Périco
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fernando Pereira Beserra
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Damião Pergentino de Sousa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. José Maria Barbosa Filho
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lucia Regina Machado da Rocha
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Clelia Akiko Hiruma-Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clelia Akiko Hiruma-Lima.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

de Carvalho, K.I.M., Bonamin, F., dos Santos, R.C. et al. Geraniol—a flavoring agent with multifunctional effects in protecting the gastric and duodenal mucosa. Naunyn-Schmiedeberg's Arch Pharmacol 387, 355–365 (2014). https://doi.org/10.1007/s00210-013-0947-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-013-0947-z

Keywords

  • Geraniol
  • Monoterpene
  • Gastric ulcer
  • Duodenal ulcer
  • Multifunctional effects