Skip to main content
SpringerLink
Log in

Beta-cyclodextrin enhanced gastroprotective effect of (−)-linalool, a monoterpene present in rosewood essential oil, in gastric lesion models

  • Brief Communication
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

(−)-Linalool is a monoterpene constituent of many essential oils. This particular monoterpene has both anti-inflammatory and antimicrobial activity. Moreover, this compound has been shown to be antinociceptive. However, the poor chemical stability and short half-life prevents the clinical application of (−)-linalool and many other essential oils. Important to the topic of this study, β-cyclodextrin (β-CD) has been used to increase the solubility, stability, and pharmacological effects of numerous lipophilic compounds in vivo. In this study, the gastroprotective activities of (−)-linalool (LIN) and linalool incorporated into inclusion complex containing β-cyclodextrin (LIN-βCD) were evaluated using models of acute and chronic gastric ulcers in rodents. LIN and LIN-βCD showed strong gastroprotective activity (p < 0.001). The LIN-βCD complex revealed that the gastroprotective effect was significantly improved compared with LIN uncomplexed, suggesting that this improvement is related to increased solubility and stability. Taking together the potentiation of the antioxidant profile of this monoterpene, our results suggest that β-CD may represent an important tool for improved gastroprotective activity of (−)-linalool and other water-insoluble compounds.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  • Arima H, Hayashi Y, Higashi T, Motoyama K (2015) Recent advances in cyclodextrin delivery techniques. Expert Opin Drug Deliv 12:1425–1441. doi:10.1517/17425247.2015.1026893

    Article  PubMed  Google Scholar 

  • Bakkali F, Averbeck S, Averbeck D, et al. (2008) Biologicl effects of essential oils—a review. Food Chem Toxicol 46:446–475. doi:10.1016/j.fct.2007.09.106

    Article  CAS  PubMed  Google Scholar 

  • Batista PA, de Paula Werner MF, Oliveira EC, et al. (2010) The antinociceptive effect of (−)-linalool in models of chronic inflammatory and neuropathic hypersensitivity in mice. J Pain 11:1222–1229. doi:10.1016/j.jpain.2010.02.022

    Article  CAS  PubMed  Google Scholar 

  • Berliocchi L, Russo R, Levato A, et al. (2009) (−)-Linalool attenuates allodynia in neuropathic pain induced by spinal nerve ligation in c57/bl6 mice. Int Rev Neurobiol 85:221–235. doi:10.1016/S0074-7742(09)85017-4

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Bradley PP, Christensen RD, Rothstein G (1982) Cellular and extracellular myeloperoxidase in pyogenic inflammation. Blood 60:618–622

    CAS  PubMed  Google Scholar 

  • Brito RG, Araújo AA, Quintans JS, et al. (2015) Enhanced analgesic activity by cyclodextrins—a systematic review and meta-analysis. Expert Opin Drug Deliv 12:1677–1688. doi:10.1517/17425247.2015.1046835

    Article  PubMed  Google Scholar 

  • Guimarães AG, Oliveira MA, Alves Rdos S, et al. (2015) Encapsulation of carvacrol, a monoterpene present in the essential oil of oregano, with β-cyclodextrin, improves the pharmacological response on cancer pain experimental protocols. Chem Biol Interact 227:69–76. doi:10.1016/j.cbi.2014.12.020

    Article  PubMed  Google Scholar 

  • Kamatou GPP, Viljoen AM (2008) Linalool—a review of a biologically active compound of commercial importance. Nat Prod Commun 3:1183–1192

    CAS  Google Scholar 

  • Kimura M, Goto S, Ihara Y, et al. (2001) Impairment of glutathione metabolism in human gastric epithelial cells treated with vacuolating cytotoxin from Helicobacter pylori. Microb Pathog 31:29–36. doi:10.1006/mpat.2001.0446

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi G, Moriya S, Wada C (2001) Deficiency of essential GTP-binding protein ObgE in Escherichia coli inhibits chromosome partition. Mol Microbiol 41(5):1037–1051

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Li WF, Huang HM, Niu XF, Fang T, Mu QL, Li HN (2013) Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice. Toxicol Appl Pharmacol 272:21–29. doi:10.1016/j.taap.2013.05.035

    Article  CAS  PubMed  Google Scholar 

  • Loftsson T, Jarho P, Masson M, Jarvinen T (2005) Cyclodextrins in drug delivery. Expert Opin. Drug Deliv 2:335–351. doi:10.1517/17425247.2.1.335

    CAS  Google Scholar 

  • Menezes PP, Serafini MR, Santana BV, et al. (2012) Solid-state β-cyclodextrin complexes containing geraniol. Thermochim Acta 548:45–50. doi:10.1016/j.tca.2012.08.023

    Article  CAS  Google Scholar 

  • Menezes PP, Serafini MR, Quintans-Junior LJ, et al. (2014) Inclusion complex of (−)-linalool and B-cyclodextrin. J Therm Anal Calorim 115:2429–2437. doi:10.1007/s10973-013-3367-x

    Article  CAS  Google Scholar 

  • Mihara M, Uchiyama M (1978) Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 86:271–278

    Article  CAS  PubMed  Google Scholar 

  • Mota KS, Dias GE, Pinto ME, Luiz-Ferreira A, Souza-Brito AR, Hiruma-Lima CA, Barbosa-Filho JM, Batista LM (2009) Flavonoids with gastroprotective activity. Molecules 14:979–1012. doi:10.3390/molecules14030979

  • Nascimento SS, Camargo EA, DeSantana JM, et al. (2014) Linalool and linalool complexed in β-cyclodextrin produce anti-hyperalgesic activity and increase Fos protein expression in animal model for fibromyalgia. Naunyn Schmiedeberg’s Arch Pharmacol 387:935–942. doi:10.1007/s00210-014-1007-z

    Article  CAS  Google Scholar 

  • Okabe S, Pfeiffer CJ (1972) Chronicity of acetic acid ulcer in the rat stomach. Am J Dig Dis 17:619–629. doi:10.1007/BF02231748

    Article  CAS  PubMed  Google Scholar 

  • Oliveira MGB, Guimarães AG, Araújo AAS, et al. (2015) Cyclodextrins: improving the therapeutic response of analgesic drugs: a patent review. Expert Opin Ther Pat 25:897–907. doi:10.1517/13543776.2015.1045412

    Article  PubMed  Google Scholar 

  • Peana AT, D’Aquila PS, Panin F, et al. (2002) Anti-inflammatory activity of linalool and linalyl acetate constituents of essential oils. Phytomedicine 9:721–726. doi:10.1078/094471102321621322

    Article  CAS  PubMed  Google Scholar 

  • Peana AT, D’Aquila PS, Chessa ML, et al. (2003) (−)-Linalool produces antinociception in two experimental models of pain. Eur J Pharmacol 460:37–41. doi:10.1016/S0014-2999(02)02856-X

    Article  CAS  PubMed  Google Scholar 

  • Peana AT, De Montis MG, Sechi S, et al. (2004) Effects of (−)-linalool in the acute hyperalgesia induced by carrageenan, L-glutamate and prostaglandin E2. Eur J Pharmacol 497:279–284. doi:10.1016/j.ejphar.2004.06.006

    Article  CAS  PubMed  Google Scholar 

  • Peana AT, Rubattu P, Piga GG, et al. (2006) Involvement of adenosine A1 and A2A receptors in (−)-linalool-induced antinociception. Life Sci 78:2471–2474. doi:10.1016/j.lfs.2005.10.025

    Article  CAS  PubMed  Google Scholar 

  • Potrich FB, Allemand A, da Silva LM, et al. (2010) Antiulcerogenic activity of hydroalcoholic extract of Achillea millefolium L.: involvement of the antioxidant system. J Ethnopharmacol 130:85–92. doi:10.1016/j.jep.2010.04.014

    Article  PubMed  Google Scholar 

  • Quintans JSS, Menezes PP, Santos MRV, et al. (2013) Improvement of p-cymene antinociceptive and anti-inflammatory effects by inclusion in β-cyclodextrin. Phytomedicine 20:436–440. doi:10.1016/j.phymed.2012.12.009

    Article  Google Scholar 

  • Quintans-Júnior LJ, Barreto RSS, Menezes PP, et al. (2013) β-cyclodextrin-complexed (−)-linalool produces antinociceptive effect superior to that of (−)-linalool in experimental pain protocols. Basic Clin Pharmacol Toxicol 113:167–172. doi:10.1111/bcpt.12087

    Article  PubMed  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

    CAS  PubMed  Google Scholar 

  • Sampaio LDFS, Maia JGS, De Parijós AM, et al. (2012) Linalool from rosewood (Aniba rosaeodora Ducke ) oil inhibits Adenylate Cyclase in the retina, contributing to understanding its biological activity. Phytother Res 77:73–77

    Article  Google Scholar 

  • Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205

    Article  CAS  PubMed  Google Scholar 

  • Serafini MR, Menezes PP, Costa LP, Lima CM, Quintans LJ Jr, Cardoso JC, et al. (2012) Interaction of p-cymene with -cyclodextrin. J Therm Anal Calorim. doi:10.1007/s10973-011-1736-x

    Google Scholar 

  • Shahin M, Konturek JW, Pohle T, et al. (2001) Remodeling of extracellular matrix in gastric ulceration. Microsc Res Tech 53:396–408. doi:10.1002/jemt.1108

    Article  CAS  PubMed  Google Scholar 

  • Sowndhararajan K, Kang SC (2013) Protective effect of ethyl acetate fraction of Acacia Ferruginea DC. against ethanol-induced gastric ulcer in rats. J Ethnopharmacol 148:175–181. doi:10.1016/j.jep.2013.04.007

    Article  PubMed  Google Scholar 

  • Tarnawski A, Tanoue K, Santos AM, Sarfeh IJ (1995) Cellular and molecular mechanisms of gastric ulcer healing. Is the quality of mucosal scar affected by treatment? Scand J Gastroenterol Suppl 210:9–14

    CAS  PubMed  Google Scholar 

  • Vonkeman HE, Fernandes RW, Van der Palen J, Van Room EN, Van der Laar MAFJ (2007) Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steroidal anti-inflammatory drugs: a nested case-control study. Arthritis Res Ther 9:1–8. doi:10.1186/ar2207

    Article  Google Scholar 

Download references

Acknowledgments

We are thankful to the UFPI (Federal University of Piauí, Brazil), UFS (Federal University of Sergipe, Brazil), and UFMG (Federal University of Minas Gerais, Brazil), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil- process number 311460/2014-3), and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil) for the financial support. Additionally, there is no conflict of interest associated with this study.

Author information

Authors and Affiliations

  1. Postgraduate Program in Biotechnology – RENORBIO, Focal Point - Federal University of Piauí, Teresina, Piauí, Brazil

    Francilene Vieira da Silva, Hélio de Barros Fernandes, Irisdalva Sousa Oliveira, Douglas Soares da Costa & Rita de Cássia Meneses Oliveira

  2. Postgraduate Program in Pharmacology, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil

    Ana Flávia Seraine Custódio Viana

  3. Laboratory of Tumoral Cell, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Miriam Teresa Paz Lopes

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

    Kamila Lopes de Lira & Rita de Cássia Meneses Oliveira

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

    Lucindo José Quintans-Júnior

  6. Department of Pharmacia, Federal University of Sergipe, Aracaju, Sergipe, Brazil

    Adriano Antunes de Sousa

Authors
  1. Francilene Vieira da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hélio de Barros Fernandes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Irisdalva Sousa Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ana Flávia Seraine Custódio Viana
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Douglas Soares da Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Miriam Teresa Paz Lopes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kamila Lopes de Lira
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lucindo José Quintans-Júnior
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Adriano Antunes de Sousa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Rita de Cássia Meneses Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rita de Cássia Meneses Oliveira.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

da Silva, F.V., de Barros Fernandes, H., Oliveira, I.S. et al. Beta-cyclodextrin enhanced gastroprotective effect of (−)-linalool, a monoterpene present in rosewood essential oil, in gastric lesion models. Naunyn-Schmiedeberg's Arch Pharmacol 389, 1245–1251 (2016). https://doi.org/10.1007/s00210-016-1298-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-016-1298-3

Keywords

Search

Navigation